RARE DISEASE
MALT lymphoma
MALT lymphoma
MALT lymphoma
Synonyms: Extranodal marginal zone B-cell lymphoma, MALToma, Mucosa-associated lymphatic tissue lymphoma, Mucosa-associated lymphoid tissue lymphoma
Synonyms: Extranodal marginal zone B-cell lymphoma, MALToma, Mucosa-associated lymphatic tissue lymphoma, Mucosa-associated lymphoid tissue lymphoma
Synonyms: Extranodal marginal zone B-cell lymphoma, MALToma, Mucosa-associated lymphatic tissue lymphoma, Mucosa-associated lymphoid tissue lymphoma
Drug discovery
11
drugs
With orphan designations
Overview
MALT lymphoma is an indolent extranodal marginal zone B-cell lymphoma primarily affecting mucosal sites, most commonly the stomach (30%), ocular adnexa (12%), and lungs (9%) [1][2][6]. Strongly associated with chronic infections (e.g., H. pylori in gastric cases) and autoimmune conditions [3][6][13], it typically presents in localized stages (60-80% cases) with nonspecific symptoms [1][6][16]. First-line management involves infection eradication for gastric cases, radiotherapy for localized disease, and chemoimmunotherapy (rituximab ± bendamustine/chlorambucil) for advanced stages [3][8][10].
Burden
Represents 5-8% of NHL [7][17]; gastric MALT constitutes 50% of primary gastric lymphomas [6]
5-year relative survival >90% [2][8]; 10-year OS >80% despite 50% 10-year relapse risk [4][8]
Significant healthcare utilization: repeated endoscopies (gastric), long-term surveillance for transformation (4% risk) [4][13]
Therapies
First-line: Antibiotics for H. pylori+ gastric cases (80% remission) [8][10]; localized disease: radiotherapy (30-34 Gy) [1][18]
Advanced: Rituximab ± chemotherapy (bendamustine/CVP); 5-year EFS 68% with R-chlorambucil [8][9]
Observation: Asymptomatic/low-burden: active monitoring preferred [5][16][12]
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
1,380 drug discovery papers about MALT lymphoma, with 13 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,380 drug discovery papers about MALT lymphoma, with 13 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-15 | A Novel Assay Platform for Targeted Protein Degradation Monitoring: Case Study of Antibody Free Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) for MALT1 Target Quantification.
The mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a central regulator of inflammatory signaling downstream of immunoreceptor tyrosine-based activation motif-containing receptors and G protein-coupled receptors (GPCRs). MALT1 has been investigated as a drug target in inflammation and cancer by inhibitors and targeted degradation. Accurate quantification of MALT1 protein is a critical unmet need for drug discovery. However, traditional ligand binding assays (LBAs), such as Enzyme-Linked Immunosorbent Assay (ELISA) or Meso Scale Discovery Assay (MSD), have been limited by the lack of suitable reagents. To address this limitation, we developed LC-MS/MS targeted MALT1 degradation monitoring assays which have enabled effective monitoring of target degradation in vivo and in vitro. A customized, reagent-independent one dimensional (1D)-LC-MS/MS assay was initially used to facilitate early-phase drug discovery screening. Furthermore, the continued progress of the discovery chemistry resulted in molecules with a higher percentage of MALT1 degradation, resulting in lower remaining MALT1 concentrations within sample matrices and the need for a highly sensitive quantitation. Consequently, a 2D-LC-MS/MS assay with a novel instrument configuration was developed. This assay has proven crucial for early drug optimization and dose selection in both in vitro and in vivo studies. The examples of assay application include the measurement of the DC50 of a lead compound across multiple species, with DC50 value of 5.2 nM in monkeys, 57.0 nM in rats, and 86.9 nM in dog splenocytes. This assay was also used to help select one of the best lead compounds with degradation showing 77.9% with in vivo treatment.
2026-08-22 | Complete remission of Helicobacter pylori-negative gastric MALT lymphoma following eradication therapy: A case report.
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is typically associated with Helicobacter pylori infection; however, approximately 10% of cases are H pylori-negative. Management guidelines differ between the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) regarding first-line treatment for these patients. Here, we report a case of H pylori-negative gastric MALT lymphoma that achieved complete remission following standard eradication therapy. A woman of Asian ethnicity in her late 50s presented with a 4-month history of intermittent, left-upper-quadrant abdominal pain. The patient had no significant medical or family history of gastric cancer or lymphoma. Upper gastrointestinal endoscopy revealed irregular whitish mucosa with ill-defined borders in the distal gastric body. Biopsies demonstrated dense lymphoid infiltrates positive for CD20, CD79a, CD43, kappa light chain, focal CD23, and CD21, with a Ki-67 index of approximately 8%, consistent with extranodal marginal zone lymphoma (MALT lymphoma). H pylori testing by 13C-urea breath test (DOB 3.5; cutoff < 4.0) and Giemsa staining was negative, although the DOB value was close to the cutoff threshold. Positron emission tomography-computed tomography and endoscopic ultrasound confirmed Lugano stage IE disease confined to the mucosa and submucosa. After multidisciplinary consultation, the patient received a 14-day bismuth-containing quadruple eradication regimen consisting of bismuth potassium citrate (2.4 g) twice daily, esomeprazole (40 mg) twice daily, amoxicillin (1 g) twice daily, and clarithromycin (0.5 g) twice daily. At 2-month follow-up, the patient was asymptomatic. Positron emission tomography-computed tomography showed no abnormalities, and repeat endoscopy with biopsies demonstrated complete histological remission, which persisted at 6-month follow-up. This case adds to the growing evidence that H pylori status alone should not preclude a trial of eradication therapy in patients with localized gastric MALT lymphoma. Potential mechanisms include the role of non-H pylori helicobacters, the direct antitumor effects of antibiotics, and immunomodulation. Larger prospective studies are needed to identify predictors of response in this population.
2026-08-19 | Role of Surgical Therapy in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma and Development of a Survival Nomogram.
This study aimed to investigate the clinical characteristics, prognostic factors, and treatment outcomes of patients with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with a diagnosis of pulmonary MALT lymphoma between 2000 and 2020. Between 2000 and 2020, a total of 1721 patients had a diagnosis of pulmonary MALT lymphoma. Among the stages I and II patients, those treated with surgery outperformed those treated with radiotherapy in survival trends, but attention should be paid to potential selection bias. Among the patients who received combination therapy, those who received surgery combined with chemotherapy had longer overall survival (OS). Multifactorial Cox regression analysis identified sex, age, Ann Arbor stage, and surgery as prognostic factors for OS. A nomogram was established for pulmonary MALT lymphoma to predict OS, with a concordance index (C-index) of 0.718 and area under curve values of 0.7235, 0.7328, and 0.7917 for the 3-, 5-, and 10-year survival rates of the nomogram, respectively, indicating that the predicted probability of the calibration curve agreed well with the actual value. Pulmonary MALT lymphoma is a type of indolent lymphoma with a good prognosis, and surgery may be associated with improved patient survival outcomes, but this association needs to be further validated in prospective studies. This study established a nomogram that has good applicability for predicting long-term OS for patients.
2026-08-10 | From Dynamics to Diagnosis and Therapy: A Multiscale Computational Framework for MALT1-Targeted Cancer Theranostics.
Cancer is one of the leading causes of death worldwide, making it a major concern in modern society. Therefore, the proposal of strategies against this illness is of major importance and has been widely studied by the scientific community in the past decades. In this sense, these strategies mainly focus on achieving improved therapy and diagnosis, with some proposals focusing on developing chemical agents capable of both treating and diagnosing cancer through targeting a cancer-related biomarker. In the role of cancer-related targets, MALT1 shows great potential as a cancer biomarker, being related to the nuclear factor-κB (NF-κB) signaling activation, an important biochemical process that regulates immune responses and inflammatory events in the human body, and its malfunction is related to the development and survival of several types of cancer. Despite MALT1's importance as a cancer target, to the best of our knowledge, there is a lack of literature proposing chemical agents capable of treating and diagnosing cancer through this biomarker. Hence, the present work's main goal was to propose a theranostic agent for this task, for which a combination of biased MD simulations, convolutional variational autoencoders (CVAEs), and quantum calculations was used. From this, it was possible to propose and optimize a compound to achieve a good MALT1 allosteric inhibition ratio while also presenting different fluorescence in different environments, crucial for signaling purposes. From this, both compounds 1 and 2 showed a cyan enol emission to blue enol emission when compared between the water-only environment and the protein environment, a feature that may serve as a molecular signature of the signaling process induced by the compound. In addition, this result also sheds light on the major relevance of enol emission of ESIPT-based probes, a few explored characteristics in the literature, which mainly focus solely on keto emission. Now, regarding inhibition, compound 1 indicated that the use of a phenothiazine derivative was a good choice, and by making a simple modification in its phenothiazine portion to generate compound 2, the inhibition ratio more than doubled, from 29% for compound 1 to 71% for compound 2, with compound 2 being an optimized chemical agent that has promising action suitable for theranostics purposes. Hence, the presented results show a promising direction toward the development of cancer theranostics drugs targeting the MALT1 allosteric pocket and provide a powerful theoretical framework that can be extended to other biological systems.
2026-07-24 | Primary extranodal marginal zone lymphoma of gastric mucosa-associated lymphoid tissue in children: a case report and review of the literature
Abstract Background Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue represents an important subtype of marginal zone lymphoma, a heterogeneous B-cell neoplasm originating from the marginal zone of lymphoid follicles. Therefore, gastric marginal zone lymphoma arising from mucosa-associated lymphoid tissue in immunocompetent children is particularly special. This article aims to report this rare case and systematically review the research progress of pediatric marginal zone lymphoma combined with its clinicopathological features. Case presentation A 13-year-old Chinese female presented with a 3-month history of recurrent epigastric pain. Gastroscopy revealed multiple ulcers in the gastric angle and antrum. Histopathological examination identified lymphoepithelial lesions and lymphoid infiltration. Immunohistochemistry showed positivity for CD20 and CD79a and negativity for CD3. PCR and capillary electrophoresis detected clonal immunoglobulin gene rearrangements, confirming monoclonality. These findings supported the diagnosis of gastric mucosa‑associated lymphoid tissue lymphoma. [ 68 Ga]Pentixafor-PET showed multiregional involvement, and Lugano stage IV was suspected (based on imaging alone, as histopathological confirmation was declined by the family). Fortunately, the patient's gastric lesions are now resolved without any discomfort after Helicobacter pylori eradication therapy. Nearly 12 months later, the patient remains on follow-up and is currently asymptomatic. Conclusions This case describes a Chinese child with pediatric gastric mucosa‑associated lymphoid tissue lymphoma with PET‑defined stage IV disease that was clearly associated with Helicobacter pylori infection. The patient achieved clinical and endoscopic remission with eradication therapy. These findings suggest that even when imaging indicates possible distant involvement, some children may still benefit from conservative treatment targeting the infection source, thereby avoiding more aggressive initial therapy (such as chemotherapy) and expanding clinical management options for such rare cases.
proteins
2024-01-26 | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation.
Introduction: Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy. Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis. Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.
2023-10-21 | Redirecting the specificity of tripartite motif containing-21 scaffolds using a novel discovery and design approach
Hijacking the ubiquitin proteasome system to elicit targeted protein degradation (TPD) has emerged as a promising therapeutic strategy to target and destroy intracellular proteins at the post-translational level. Small molecule-based TPD approaches, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, have shown potential, with several agents currently in clinical trials. Biological PROTACs (bioPROTACs), which are engineered fusion proteins comprised of a target-binding domain and an E3 ubiquitin ligase, have emerged as a complementary approach for TPD. Here, we describe a new method for the evolution and design of bioPROTACs. Specifically, engineered binding scaffolds based on the third fibronectin type III domain of human tenascin-C (Tn3) were installed into the E3 ligase tripartite motif containing-21 (TRIM21) to redirect its degradation specificity. This was achieved via selection of naïve yeast-displayed Tn3 libraries against two different oncogenic proteins associated with B-cell lymphomas, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) and embryonic ectoderm development protein (EED), and replacing the native substrate-binding domain of TRIM21 with our evolved Tn3 domains. The resulting TRIM21-Tn3 fusion proteins retained the binding properties of the Tn3 as well as the E3 ligase activity of TRIM21. Moreover, we demonstrated that TRIM21-Tn3 fusion proteins efficiently degraded their respective target proteins through the ubiquitin proteasome system in cellular models. We explored the effects of binding domain avidity and E3 ligase utilization to gain insight into the requirements for effective bioPROTAC design. Overall, this study presents a versatile engineering approach that could be used to design and engineer TRIM21-based bioPROTACs against therapeutic targets.
2020-09-24 | Use of Non-Natural Amino Acids for the Design and Synthesis of a Selective, Cell-Permeable MALT1 Activity-Based Probe.
Constitutive proteolytic activity of MALT1 is associated with highly aggressive B-cell lymphomas. Chemical tools that detect active MALT1 have been reported, but suffer from poor cell permeability and/or cross-reactivity with the cysteine protease cathepsin B. Here, we report that the non-natural amino acid pipecolinic acid in the P2 position of substrates and chemical probes leads to improved selectivity toward MALT1 and results in cell-permeable fluorescent probes.
2020-05-11 | Allosteric activation of MALT1 by its ubiquitin-binding Ig3 domain.
The catalytic activity of the protease MALT1 is required for adaptive immune responses and regulatory T (Treg)-cell development, while dysregulated MALT1 activity can lead to lymphoma. MALT1 activation requires its monoubiquitination on lysine 644 (K644) within the Ig3 domain, localized adjacent to the protease domain. The molecular requirements for MALT1 monoubiquitination and the mechanism by which monoubiquitination activates MALT1 had remained elusive. Here, we show that the Ig3 domain interacts directly with ubiquitin and that an intact Ig3-ubiquitin interaction surface is required for the conjugation of ubiquitin to K644. Moreover, by generating constitutively active MALT1 mutants that overcome the need for monoubiquitination, we reveal an allosteric communication between the ubiquitination site K644, the Ig3-protease interaction surface, and the active site of the protease domain. Finally, we show that MALT1 mutants that alter the Ig3-ubiquitin interface impact the biological response of T cells. Thus, ubiquitin binding by the Ig3 domain promotes MALT1 activation by an allosteric mechanism that is essential for its biological function.
2019-10-24 | Determination of extended substrate specificity of the MALT1 as a strategy for the design of potent substrates and activity-based probes.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) belongs to the CD clan of cysteine proteases. MALT1 is a unique enzyme among this clan because it recognizes the basic amino acid arginine in the P1 pocket. Previous studies carried out with natural amino acids revealed the substrate specificity of the P4-P1 pockets of MALT1 but have provided only limited information about the catalytic preferences of this enzyme. In this study, we exploited Hybrid Combinatorial Substrate Library and Internally Quenched Fluorescence substrate technologies to interrogate the extended substrate specificity profile of the S5-S2' active site pockets using unnatural amino acids. This strategy resulted in the design of a peptide-based fluorogenic substrate, which exhibited significant activity toward MALT1. Subsequently, the substrate sequence was further utilized to develop potent, irreversible activity-based probes.
antibodies
2026-09-13 | Primary Extranodal Marginal Zone Lymphoma of the Breast: A Case Report Highlighting the Clinicopathological Paradigm of an Indolent B-Cell Neoplasm
Primary or secondary lymphoma of the breast is an uncommon entity, accounting for less than 0.5% of all breast malignancies and approximately 1-2% of extranodal lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) is the most frequently reported histological subtype. Marginal zone B-cell lymphoma involving the breast is exceedingly rare, particularly in patients with a prior history of DLBCL. The present case describes an unusual occurrence of synchronous second primary lymphoid neoplasm of breast in a patient previously treated for DLBCL, highlighting its diagnostic rarity. The authors report a rare case of a 57-year-old female with a past history of DLBCL, diagnosed two years ago on histopathological examination of excised lymph node over left neck region. Patient received chemoradiotherapy post-diagnosis and had recovered completely. She now presented with bilateral breast lumps and an additional lump in the left axillary region. An initial histopathological diagnosis of Non-Hodgkin’s Lymphoma of breast was made which needed further immunophenotypic characterisation. Immunohistochemistry (IHC) was done which showed strong positivity for CD45, CD19, CD20, PAX5, Bcl2, Ki-67 which confirmed the diagnosis of Marginal Zone B-cell Lymphoma, emphasising diagnostic challenges. Post histopathological diagnosis and immunohistochemistry, patient received targeted therapy along with chemotherapy to which she responded well. The present case is noteworthy because of the uncommon involvement of both breasts and the axillary region in a patient with a prior diagnosis of DLBCL, suggesting potential disease recurrence or extranodal extension.
2026-08-14 | Small Intestinal Extranodal Marginal Zone Lymphoma Mimicking Crohn's Disease.
Inflammatory bowel disease (IBD) mimics pose a significant diagnostic challenge, particularly in patients with atypical features or refractory disease. Intestinal lymphomas, especially extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, can closely resemble Crohn's disease clinically, endoscopically, and histologically. We report a 23-year-old woman with a 2-year history of chronic, large-volume diarrhea, weight loss, and malabsorption, initially diagnosed and treated as Crohn's disease. Despite corticosteroids, azathioprine, and biologic therapy, she demonstrated only a partial response. Further evaluation revealed hypoalbuminemia, elevated inflammatory markers, and monoclonal gammopathy on serum protein electrophoresis. Endoscopic and radiological findings showed ileal and jejunal involvement. Histopathological examination demonstrated a dense lymphoplasmacytic infiltrate, and immunohistochemistry revealed CD20 and CD138 positivity with light chain restriction. A final diagnosis of small intestinal extranodal marginal zone lymphoma was established. The patient was treated with combined chemotherapy, with plans to escalate to rituximab-based therapy due to a suboptimal response. This case highlights the importance of reconsidering the diagnosis in patients with presumed IBD who exhibit atypical features, such as severe malabsorption, proximal small bowel involvement, monoclonal gammopathy, or refractory disease. Early recognition of IBD mimics, particularly intestinal lymphomas, is critical to ensure appropriate management and improve outcomes.
2026-07-17 | Dose-reduced (24 Gy) involved-site radiotherapy combined with rituximab in early-stage non-gastric mucosa-associated lymphoid tissue lymphoma: a prospective phase II trial.
While involved-site radiotherapy (ISRT) is the standard first-line treatment in localized non-gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the cumulative risk of distant relapse poses a persistent clinical challenge. We conducted a prospective phase II trial evaluating rituximab with 24 Gy ISRT, aiming to reduce distant relapse and enhance long-term survival. By October 2025, 60 patients with early-stage non-gastric MALT lymphoma were enrolled. Among the per-protocol efficacy-evaluable cohort (n = 55), the combined immunoradiotherapy regimen achieved a complete response rate of 100%. At a median follow-up of 30.2 months, only one distant recurrence was observed (estimated 5-year distant recurrence: 1.9%). In the full analysis set, 2- and 4-year progression-free survival rates were 98.0% and 92.9%, respectively, improving to 100% and 94.4% in the per-protocol set. Treatment-related hematologic toxicity was frequent but manageable. Infections were reported in 23.3%, including one grade 4 respiratory infection that necessitated treatment discontinuation. Immunophenotypic profiling revealed that parotid, thyroid, or mediastinal involvement correlated with higher lymphocyte proportions (39.5% ± 16.4%, P = 0.012). Post-treatment immunologic changes featured near-complete B-cell depletion and a compensatory expansion of NK cells. Overall, the combined immunoradiotherapy regimen demonstrated durable disease control in localized non-gastric MALT lymphoma, with potential synergistic benefit from NK cell-mediated immune activation. Trial registration: Chinese Clinical Trials Registry, ChiCTR2000036318; registered on Aug 22, 2020 (prospective).
2026-05-14 | Primary pulmonary mucosa-associated lymphoid tissue lymphoma with nodular pulmonary amyloidosis
82歳女性．胸部CT検査で偶然左肺S8末梢に径22 mmの空洞性結節病変を指摘された．経時的に増大傾向であり，原発性左下葉肺癌（cT1cN0M0，c-StageIA3）を疑い，診断および治療目的にロボット支援下左肺下葉切除およびリンパ節郭清（ND2a-1）を行った．腫瘤は褐色結節で病理組織学的には好酸性沈着物を認め，異物巨細胞浸潤や軽度の線維化，骨形成を伴っていた．好酸性沈着物はDFS染色陽性で過マンガン酸処理で染色性は消失せず，結節性肺アミロイドーシスの病理組織像だった．一方で辺縁は小型～中型のリンパ球や形質細胞が密に浸潤しており，免疫染色でCD20が陽性，CD43が一部陽性だった．さらに免疫グロブリン軽鎖はλ鎖優位の軽鎖制限を認め，結節性肺アミロイドーシスを合併した肺原発mucosa-associated lymphoid tissue（MALT）リンパ腫と診断した．
2026-04-09 | Treatment and outcomes of pulmonary mucosa-associated lymphoid tissue lymphoma: A multicenter analysis of 186 patients.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with pulmonary involvement is a rare, indolent lymphoma with no standard treatment approaches. To clarify patient characteristics, treatment, and prognosis of pulmonary MALT lymphoma in the modern era, a multi-institutional observational study of patients diagnosed between 2013 and 2022 was conducted. A modified Ann Arbor system was used for the analysis. Among 186 eligible patients, 131 (70%) had stage IE/IIE disease, whereas 55 (30%) had stage IV disease. No patient had stage III disease. With a median follow-up of 57 months, the 4-year overall survival (OS) rates for the stage IE, IIE, and IV groups were 96%, 92%, and 90%, respectively. The stage IIE and IV groups had similar progression-free survival (PFS) that was significantly worse than that of the stage IE group (p < .001). In stage IE/IIE patients, no differences were found in OS (p = .89) or PFS (p = .90) among the first-line treatment groups. In stage IV patients, the stomach was the most common synchronous extranodal site of involvement (36%). There were no differences in OS among the first-line treatment groups (p = .64). The OS of patients with MALT lymphoma with pulmonary involvement was favorable regardless of first-line treatment modality, including watchful waiting. The short PFS in the stage IIE and IV groups indicates that these groups are candidates for therapeutic development.
oligonucleotides
2025-10-05 | A prophylactic study of curcumin nanoparticle-induced bacterial ghosts against Helicobacter pylori in a C57BL/6 mouse model.
Gastro-duodenal diseases are becoming a chronic health burden worldwide. Helicobacter pylori plays a key role in developing gastro-duodenal disorders including dyspepsia, peptic ulcers, gastritis and MALT lymphoma. It is the major cause of stomach cancer due to infectious agents (IARC, 2020). Inefficiency of proper diagnostic approaches and reduced efficacy of existing treatments are leading to an increase in antimicrobial resistance (AMR) sharply. The development of a vaccine calls for the isolation of a potent immunogen sufficient to induce a robust immune response by activating both humoral and cellular arms of immunity. Bacterial ghost is a membrane-bound empty capsule embedded with various antigens and is an emerging next generation vaccine candidate. Curcumin, the major bioactive component of the herb turmeric, is known to have an anti-Helicobacter pylori effect, indicating its therapeutic potential as an alternative treatment. Formulation of curcumin nanoparticles alters its biophysical properties without affecting its chemical integrity, allowing the preparation of a suspension with a heterogeneous particle population. In vitro, curcumin nanoparticle-induced bacterial ghost cells (CurBGs) showed considerably reduced cytotoxicity. Serum IgG as well as its subtypes IgG1 and IgG2c were significantly evoked by three consecutive oral immunizations. Furthermore, a strong immunogen-specific response was produced in immunized animals, which may provide cross-protection regardless of the circulating H. pylori strains' cag (cytotoxin-associated gene) status. Therefore, curcumin nanoparticles treated bacterial ghosts can be an excellent novel ghost-based vaccine candidate, potentially reducing the H. pylori-mediated clinical health burden worldwide in the near future.
2025-03-13 | Targeting both death and paracaspase domains of MALT1 with antisense oligonucleotides overcomes resistance to immune-checkpoint inhibitors.
Targeting MALT1's paracaspase activity has been explored for B cell lymphoma and solid tumors. While the role of MALT1 in promoting cancer cell proliferation has been investigated, its involvement in immune evasion is unclear. Here we report that MALT1 promotes immune evasion through its paracaspase and death domain. In a paracaspase-dependent manner, MALT1 protects CD274 mRNA from degradation by its cleavage of ROQUIN1 and ROQUIN2. In a death-domain-dependent manner, MALT1 promotes the proliferation and polarization of tumor-associated macrophages to generate an immunosuppressive tumor microenvironment. Targeting MALT1 with antisense oligonucleotides inhibits PD-L1 expression in patient-derived tumor cells and suppresses the proliferation and M2-like polarization of tumor-associated macrophages isolated from patients with cancer. In preclinical models of solid tumors in female mice, treatment with MALT1 antisense oligonucleotides overcomes resistance to immune-checkpoint inhibitors. Together, our study demonstrates that targeting MALT1 is a potential strategy to overcome immune-checkpoint inhibitor resistance.
2023-05-05 | Uncovering the role of microRNA671-5p/CDCA7L/monoamine oxidase-A signaling in Helicobacter pylori mediated apoptosis in gastric epithelial cells.
Helicobacter pylori is a gram-negative microaerophilic bacterium and is associated with gastrointestinal diseases ranging from peptic ulcer and gastritis to gastric cancer and mucosa-associated lymphoid tissue lymphoma. In our laboratory, the transcriptomes and miRnomes of AGS cells infected with H. pylori have been profiled, and an miRNA-mRNA network has been constructed. MicroRNA 671-5p is upregulated during H. pylori infection of AGS cells or of mice. In this study, the role of miR-671-5p during infection has been investigated. It has been validated that miR-671-5p targets the transcriptional repressor CDCA7L, which is downregulated during infection (in vitro and in vivo) concomitant with miR-671-5p upregulation. Further, it has been established that the expression of monoamine oxidase A (MAO-A) is repressed by CDCA7L, and that MAO-A triggers the generation of reactive oxygen species (ROS). Consequently, miR-671-5p/CDCA7L signaling is linked to the generation of ROS during H. pylori infection. Finally, it has been demonstrated that ROS-mediated caspase 3 activation and apoptosis that occurs during H. pylori infection, is dependent on the miR-671-5p/CDCA7L/MAO-A axis. Based on the above reports, it is suggested that targeting miR-671-5p could offer a means of regulating the course and consequences of H. pylori infection.
2023-03-29 | Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1β, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.
2022-12-08 | Identifying tumor antigens and immune subtypes of gastrointestinal MALT lymphoma for immunotherapy development
MALT lymphoma is an extranodal B-cell lymphoma of the marginal zone of mucosa-associated lymphoid tissue (MALT), caused by malignant transformation of B-cells in the marginal zone. In this work, we aim to explore the potential relationship between MALT lymphoma and DLBCL. Vaccines derived from messenger ribonucleic acid (mRNA) may provide satisfactory results. Despite being a promising treatment option, immunotherapy isn't widely used in treating renal cell carcinoma, as only a few patients respond to the treatment. The Cancer Genome Atlas (TCGA) analysis revealed gene expression profiles and clinical information. Antigen-presenting cells infiltrated the immune system using TIMER tool (http://timer.cistrome.org/). GDSC (Genomics of Drug Sensitivity in Cancer) data were used to estimate drug sensitivity. Immune-related genes were associated with a better prognosis in MALT lymphoma patients and higher levels of antigen-presenting cells. There is a significant relationship between these immune subtypes and immunological checkpoints, immunogenic cell death regulators, and prognostic variables for MALT lymphoma patients. In this study, we provide a theoretical foundation for the development of mRNA vaccines and suggest that KLHL14 could potentially be used as antigens to develop mRNA vaccines for MALT lymphoma.
other
2026-08-12 | MALT1 alternative splicing-A molecular rheostat for balancing immune activation and homeostasis.
MALT1 (mucosa-associated lymphoid tissue lymphoma/leukemia protein 1)-TRAF6 [tumor necrosis factor receptor (TNFR)-associated factor 6] interaction drives lymphocyte activation and adaptive immunity, but it also contributes to maintaining immune homeostasis. MALT1 exists in two isoforms that differ only by either encoding two (MALT1A) or one (MALT1B) TRAF6 binding motif (T6BM). The human mutation MALT1 E806D in T6BM2, expressed in both MALT1A and MALT1B, has been associated with an immune disorder combining symptoms of immune deficiency and autoimmunity. Here, we report that the orthologous germline mutation MALT1 E814D is sufficient to induce a fatal autoimmune syndrome in mice. We demonstrate that species-specific differences in the effects of T6BM2 disruptions can be attributed to alterations in MALT1 splicing and that immune homeostasis is restored by genetically enforcing expression of MALT1A in MALT1 E814D mice. Thus, alternative MALT1 splicing allows tuning of TRAF6 association, thereby functioning as a molecular rheostat to balance between optimal immune activation and maintenance of peripheral tolerance.
2025-08-01 | Loss of MALT1 Function in a Patient With Combined Immunodeficiency: a Novel Pathogenic Variant and Immunological Insights.
Germline pathogenic variants in the mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) encodes a caspase-like protease that plays a crucial role in the caspase recruitment domain (CARD)-B-cell lymphoma 10 (BCL10)-MALT1 (CBM) complex. This complex mediates the activation of nuclear factor-kB (NF-kB) pathway and are associated with diverse human diseases including combine immunodeficiency (CID), lymphoproliferation and others. This study aimed to determine the underlying cause of immune deficiency and immune dysregulation in a patient presented with recurrent respiratory infections, aphthous ulcers, dermatitis, chronic diarrhea, failure to thrive and early death. Clinical and laboratory records were reviewed. Patients underwent next-generation sequencing (NGS), and analysis of genomic DNA was performed on the patient and her parents. Lymphocyte subsets, MALT1 expression and NF-kB signaling was evaluated by flow cytometry, RT-PCR and immunoblotting. The patient carried a novel pathogenic biallelic loss-of-function variant in MALT1 (c.1411G > A; p.D471N) located in the caspase-like domain, leading to severely reduced MALT1 protein expression. Impaired CBM-mediated NF-κB activation was confirmed by reduced phosphorylation of the p65 subunit, resulting in deficient production of IL-2 and TNF-α. This functional defect caused lower Tfr and Treg cells, a normal proportion of Tfh cells, with higher expression of activation markers PD-1 and ICOS. The patient displayed low NK cell and B cell counts, together with a developmental block at the transitional B cell stage. Additionally, the proportion of marginal zone-like B cells (MZB-like) was markedly decreased, indicating impaired B cell differentiation. Human MALT1 deficiency causes profound CID by impairing CBM-mediated NF-kB signaling and MALT1-paracaspase activity. Consistent with the reported variants located in the caspase-like domain, our patient presented with an inflammatory phenotype, supporting the notion that the MALT1 D471N mutation phenocopies a partial loss of both MALT1 scaffolding function and paracaspase activity. Prompt hematopoietic stem cell transplantation (HSCT) is highly recommended as an effective therapy for MALT1 deficiency.
2025-06-01 | Marginal Zone Lymphoma: Treatment Update With a Focus on Systemic Approaches
Marginal zone lymphoma (MZL) is the second most common indolent B-cell lymphoma and comprised of three clinical subtypes based on site of involvement: extranodal marginal zone lymphoma (usually of mucosa-associated lymphoid tissue), nodal marginal zone lymphoma, and splenic marginal zone lymphoma (often with circulating villous lymphocytes). MZL is the prototype for an antigen-driven malignancy, and there are clear areas where elimination of the antigenic trigger leads to lymphoma regression. Although there is an excellent prognosis, the disease remains incurable, and the majority of patients will need repeated therapy for disease control over the course of their lifetime. Current treatment paradigms include rituximab monotherapy and chemoimmunotherapy in the frontline setting. In the relapsed or refractory setting, there are exciting advances including the recent approval of the covalent BTK inhibitor, zanubrutinib. Emerging therapies include CAR-T cell and T-cell engaging bispecific antibodies, with promising early results. This primer on MZL will discuss the three subtypes and focus on treatment approaches in the treatment-naïve and relapsed/refractory setting.
2025-03-30 | [Update on marginal zone lymphoma classification, diagnosis and treatment in 2024].
Marginal zone lymphoma (MZL) is the third most frequent lymphoma in Western countries with an increasing incidence with age. There are different histologic subtypes: Splenic MZL (SMZL), Nodal MZL (NZML), Extranodal MZL (EMZL) or MALT lymphoma and more recently, a novel entity called splenic diffuse red pulp small B-cell lymphoma. The accurate diagnosis relies on morphologic, phenotypic, cytogenetic and molecular features in order to rule out other indolent non-Hodgkin lymphomas. First line treatment depends on MZL subtypes: depending on localized or disseminated disease, MALT lymphoma are managed with radiotherapy on immunochemotherapy. SMZL, when requiring therapy, are treated with splenectomy ore more frequently monotherapy Rituximab or immunochemotherapy depending on age, comorbidities and tumor burden. Management of NMZL is often similar to Follicular lymphoma treatment. Treatment of refractory or relapsed MZL takes into account the time between the diagnosis and the progression, the nature and outcomes of previous therapies and the general condition of the patient. Conventional treatments may be a suitable option but novel therapies are more frequently used. In this review, we focus on the role of Bruton Tyrosine Kinases (where only Zanubrutinib has marketing authorization in France), PI3Kinases, Syk and BCL-2 inhibitors as well as on the results of immunomodulatory drugs and more recently the use of bispecific antibodies and T-cell chimeric antigen receptor (CAR-T cell).
2024-02-26 | Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting
Helicobacter pylori ( H. pylori ) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori , underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections.
small molecules
2026-09-15 | A Novel Assay Platform for Targeted Protein Degradation Monitoring: Case Study of Antibody Free Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) for MALT1 Target Quantification.
The mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a central regulator of inflammatory signaling downstream of immunoreceptor tyrosine-based activation motif-containing receptors and G protein-coupled receptors (GPCRs). MALT1 has been investigated as a drug target in inflammation and cancer by inhibitors and targeted degradation. Accurate quantification of MALT1 protein is a critical unmet need for drug discovery. However, traditional ligand binding assays (LBAs), such as Enzyme-Linked Immunosorbent Assay (ELISA) or Meso Scale Discovery Assay (MSD), have been limited by the lack of suitable reagents. To address this limitation, we developed LC-MS/MS targeted MALT1 degradation monitoring assays which have enabled effective monitoring of target degradation in vivo and in vitro. A customized, reagent-independent one dimensional (1D)-LC-MS/MS assay was initially used to facilitate early-phase drug discovery screening. Furthermore, the continued progress of the discovery chemistry resulted in molecules with a higher percentage of MALT1 degradation, resulting in lower remaining MALT1 concentrations within sample matrices and the need for a highly sensitive quantitation. Consequently, a 2D-LC-MS/MS assay with a novel instrument configuration was developed. This assay has proven crucial for early drug optimization and dose selection in both in vitro and in vivo studies. The examples of assay application include the measurement of the DC50 of a lead compound across multiple species, with DC50 value of 5.2 nM in monkeys, 57.0 nM in rats, and 86.9 nM in dog splenocytes. This assay was also used to help select one of the best lead compounds with degradation showing 77.9% with in vivo treatment.
2026-08-22 | Complete remission of Helicobacter pylori-negative gastric MALT lymphoma following eradication therapy: A case report.
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is typically associated with Helicobacter pylori infection; however, approximately 10% of cases are H pylori-negative. Management guidelines differ between the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) regarding first-line treatment for these patients. Here, we report a case of H pylori-negative gastric MALT lymphoma that achieved complete remission following standard eradication therapy. A woman of Asian ethnicity in her late 50s presented with a 4-month history of intermittent, left-upper-quadrant abdominal pain. The patient had no significant medical or family history of gastric cancer or lymphoma. Upper gastrointestinal endoscopy revealed irregular whitish mucosa with ill-defined borders in the distal gastric body. Biopsies demonstrated dense lymphoid infiltrates positive for CD20, CD79a, CD43, kappa light chain, focal CD23, and CD21, with a Ki-67 index of approximately 8%, consistent with extranodal marginal zone lymphoma (MALT lymphoma). H pylori testing by 13C-urea breath test (DOB 3.5; cutoff < 4.0) and Giemsa staining was negative, although the DOB value was close to the cutoff threshold. Positron emission tomography-computed tomography and endoscopic ultrasound confirmed Lugano stage IE disease confined to the mucosa and submucosa. After multidisciplinary consultation, the patient received a 14-day bismuth-containing quadruple eradication regimen consisting of bismuth potassium citrate (2.4 g) twice daily, esomeprazole (40 mg) twice daily, amoxicillin (1 g) twice daily, and clarithromycin (0.5 g) twice daily. At 2-month follow-up, the patient was asymptomatic. Positron emission tomography-computed tomography showed no abnormalities, and repeat endoscopy with biopsies demonstrated complete histological remission, which persisted at 6-month follow-up. This case adds to the growing evidence that H pylori status alone should not preclude a trial of eradication therapy in patients with localized gastric MALT lymphoma. Potential mechanisms include the role of non-H pylori helicobacters, the direct antitumor effects of antibiotics, and immunomodulation. Larger prospective studies are needed to identify predictors of response in this population.
2026-08-19 | Role of Surgical Therapy in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma and Development of a Survival Nomogram.
This study aimed to investigate the clinical characteristics, prognostic factors, and treatment outcomes of patients with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with a diagnosis of pulmonary MALT lymphoma between 2000 and 2020. Between 2000 and 2020, a total of 1721 patients had a diagnosis of pulmonary MALT lymphoma. Among the stages I and II patients, those treated with surgery outperformed those treated with radiotherapy in survival trends, but attention should be paid to potential selection bias. Among the patients who received combination therapy, those who received surgery combined with chemotherapy had longer overall survival (OS). Multifactorial Cox regression analysis identified sex, age, Ann Arbor stage, and surgery as prognostic factors for OS. A nomogram was established for pulmonary MALT lymphoma to predict OS, with a concordance index (C-index) of 0.718 and area under curve values of 0.7235, 0.7328, and 0.7917 for the 3-, 5-, and 10-year survival rates of the nomogram, respectively, indicating that the predicted probability of the calibration curve agreed well with the actual value. Pulmonary MALT lymphoma is a type of indolent lymphoma with a good prognosis, and surgery may be associated with improved patient survival outcomes, but this association needs to be further validated in prospective studies. This study established a nomogram that has good applicability for predicting long-term OS for patients.
2026-08-10 | From Dynamics to Diagnosis and Therapy: A Multiscale Computational Framework for MALT1-Targeted Cancer Theranostics.
Cancer is one of the leading causes of death worldwide, making it a major concern in modern society. Therefore, the proposal of strategies against this illness is of major importance and has been widely studied by the scientific community in the past decades. In this sense, these strategies mainly focus on achieving improved therapy and diagnosis, with some proposals focusing on developing chemical agents capable of both treating and diagnosing cancer through targeting a cancer-related biomarker. In the role of cancer-related targets, MALT1 shows great potential as a cancer biomarker, being related to the nuclear factor-κB (NF-κB) signaling activation, an important biochemical process that regulates immune responses and inflammatory events in the human body, and its malfunction is related to the development and survival of several types of cancer. Despite MALT1's importance as a cancer target, to the best of our knowledge, there is a lack of literature proposing chemical agents capable of treating and diagnosing cancer through this biomarker. Hence, the present work's main goal was to propose a theranostic agent for this task, for which a combination of biased MD simulations, convolutional variational autoencoders (CVAEs), and quantum calculations was used. From this, it was possible to propose and optimize a compound to achieve a good MALT1 allosteric inhibition ratio while also presenting different fluorescence in different environments, crucial for signaling purposes. From this, both compounds 1 and 2 showed a cyan enol emission to blue enol emission when compared between the water-only environment and the protein environment, a feature that may serve as a molecular signature of the signaling process induced by the compound. In addition, this result also sheds light on the major relevance of enol emission of ESIPT-based probes, a few explored characteristics in the literature, which mainly focus solely on keto emission. Now, regarding inhibition, compound 1 indicated that the use of a phenothiazine derivative was a good choice, and by making a simple modification in its phenothiazine portion to generate compound 2, the inhibition ratio more than doubled, from 29% for compound 1 to 71% for compound 2, with compound 2 being an optimized chemical agent that has promising action suitable for theranostics purposes. Hence, the presented results show a promising direction toward the development of cancer theranostics drugs targeting the MALT1 allosteric pocket and provide a powerful theoretical framework that can be extended to other biological systems.
2026-07-24 | Primary extranodal marginal zone lymphoma of gastric mucosa-associated lymphoid tissue in children: a case report and review of the literature
Abstract Background Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue represents an important subtype of marginal zone lymphoma, a heterogeneous B-cell neoplasm originating from the marginal zone of lymphoid follicles. Therefore, gastric marginal zone lymphoma arising from mucosa-associated lymphoid tissue in immunocompetent children is particularly special. This article aims to report this rare case and systematically review the research progress of pediatric marginal zone lymphoma combined with its clinicopathological features. Case presentation A 13-year-old Chinese female presented with a 3-month history of recurrent epigastric pain. Gastroscopy revealed multiple ulcers in the gastric angle and antrum. Histopathological examination identified lymphoepithelial lesions and lymphoid infiltration. Immunohistochemistry showed positivity for CD20 and CD79a and negativity for CD3. PCR and capillary electrophoresis detected clonal immunoglobulin gene rearrangements, confirming monoclonality. These findings supported the diagnosis of gastric mucosa‑associated lymphoid tissue lymphoma. [ 68 Ga]Pentixafor-PET showed multiregional involvement, and Lugano stage IV was suspected (based on imaging alone, as histopathological confirmation was declined by the family). Fortunately, the patient's gastric lesions are now resolved without any discomfort after Helicobacter pylori eradication therapy. Nearly 12 months later, the patient remains on follow-up and is currently asymptomatic. Conclusions This case describes a Chinese child with pediatric gastric mucosa‑associated lymphoid tissue lymphoma with PET‑defined stage IV disease that was clearly associated with Helicobacter pylori infection. The patient achieved clinical and endoscopic remission with eradication therapy. These findings suggest that even when imaging indicates possible distant involvement, some children may still benefit from conservative treatment targeting the infection source, thereby avoiding more aggressive initial therapy (such as chemotherapy) and expanding clinical management options for such rare cases.
proteins
2024-01-26 | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation.
Introduction: Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy. Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis. Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.
2023-10-21 | Redirecting the specificity of tripartite motif containing-21 scaffolds using a novel discovery and design approach
Hijacking the ubiquitin proteasome system to elicit targeted protein degradation (TPD) has emerged as a promising therapeutic strategy to target and destroy intracellular proteins at the post-translational level. Small molecule-based TPD approaches, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, have shown potential, with several agents currently in clinical trials. Biological PROTACs (bioPROTACs), which are engineered fusion proteins comprised of a target-binding domain and an E3 ubiquitin ligase, have emerged as a complementary approach for TPD. Here, we describe a new method for the evolution and design of bioPROTACs. Specifically, engineered binding scaffolds based on the third fibronectin type III domain of human tenascin-C (Tn3) were installed into the E3 ligase tripartite motif containing-21 (TRIM21) to redirect its degradation specificity. This was achieved via selection of naïve yeast-displayed Tn3 libraries against two different oncogenic proteins associated with B-cell lymphomas, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) and embryonic ectoderm development protein (EED), and replacing the native substrate-binding domain of TRIM21 with our evolved Tn3 domains. The resulting TRIM21-Tn3 fusion proteins retained the binding properties of the Tn3 as well as the E3 ligase activity of TRIM21. Moreover, we demonstrated that TRIM21-Tn3 fusion proteins efficiently degraded their respective target proteins through the ubiquitin proteasome system in cellular models. We explored the effects of binding domain avidity and E3 ligase utilization to gain insight into the requirements for effective bioPROTAC design. Overall, this study presents a versatile engineering approach that could be used to design and engineer TRIM21-based bioPROTACs against therapeutic targets.
2020-09-24 | Use of Non-Natural Amino Acids for the Design and Synthesis of a Selective, Cell-Permeable MALT1 Activity-Based Probe.
Constitutive proteolytic activity of MALT1 is associated with highly aggressive B-cell lymphomas. Chemical tools that detect active MALT1 have been reported, but suffer from poor cell permeability and/or cross-reactivity with the cysteine protease cathepsin B. Here, we report that the non-natural amino acid pipecolinic acid in the P2 position of substrates and chemical probes leads to improved selectivity toward MALT1 and results in cell-permeable fluorescent probes.
2020-05-11 | Allosteric activation of MALT1 by its ubiquitin-binding Ig3 domain.
The catalytic activity of the protease MALT1 is required for adaptive immune responses and regulatory T (Treg)-cell development, while dysregulated MALT1 activity can lead to lymphoma. MALT1 activation requires its monoubiquitination on lysine 644 (K644) within the Ig3 domain, localized adjacent to the protease domain. The molecular requirements for MALT1 monoubiquitination and the mechanism by which monoubiquitination activates MALT1 had remained elusive. Here, we show that the Ig3 domain interacts directly with ubiquitin and that an intact Ig3-ubiquitin interaction surface is required for the conjugation of ubiquitin to K644. Moreover, by generating constitutively active MALT1 mutants that overcome the need for monoubiquitination, we reveal an allosteric communication between the ubiquitination site K644, the Ig3-protease interaction surface, and the active site of the protease domain. Finally, we show that MALT1 mutants that alter the Ig3-ubiquitin interface impact the biological response of T cells. Thus, ubiquitin binding by the Ig3 domain promotes MALT1 activation by an allosteric mechanism that is essential for its biological function.
2019-10-24 | Determination of extended substrate specificity of the MALT1 as a strategy for the design of potent substrates and activity-based probes.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) belongs to the CD clan of cysteine proteases. MALT1 is a unique enzyme among this clan because it recognizes the basic amino acid arginine in the P1 pocket. Previous studies carried out with natural amino acids revealed the substrate specificity of the P4-P1 pockets of MALT1 but have provided only limited information about the catalytic preferences of this enzyme. In this study, we exploited Hybrid Combinatorial Substrate Library and Internally Quenched Fluorescence substrate technologies to interrogate the extended substrate specificity profile of the S5-S2' active site pockets using unnatural amino acids. This strategy resulted in the design of a peptide-based fluorogenic substrate, which exhibited significant activity toward MALT1. Subsequently, the substrate sequence was further utilized to develop potent, irreversible activity-based probes.
antibodies
2026-09-13 | Primary Extranodal Marginal Zone Lymphoma of the Breast: A Case Report Highlighting the Clinicopathological Paradigm of an Indolent B-Cell Neoplasm
Primary or secondary lymphoma of the breast is an uncommon entity, accounting for less than 0.5% of all breast malignancies and approximately 1-2% of extranodal lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) is the most frequently reported histological subtype. Marginal zone B-cell lymphoma involving the breast is exceedingly rare, particularly in patients with a prior history of DLBCL. The present case describes an unusual occurrence of synchronous second primary lymphoid neoplasm of breast in a patient previously treated for DLBCL, highlighting its diagnostic rarity. The authors report a rare case of a 57-year-old female with a past history of DLBCL, diagnosed two years ago on histopathological examination of excised lymph node over left neck region. Patient received chemoradiotherapy post-diagnosis and had recovered completely. She now presented with bilateral breast lumps and an additional lump in the left axillary region. An initial histopathological diagnosis of Non-Hodgkin’s Lymphoma of breast was made which needed further immunophenotypic characterisation. Immunohistochemistry (IHC) was done which showed strong positivity for CD45, CD19, CD20, PAX5, Bcl2, Ki-67 which confirmed the diagnosis of Marginal Zone B-cell Lymphoma, emphasising diagnostic challenges. Post histopathological diagnosis and immunohistochemistry, patient received targeted therapy along with chemotherapy to which she responded well. The present case is noteworthy because of the uncommon involvement of both breasts and the axillary region in a patient with a prior diagnosis of DLBCL, suggesting potential disease recurrence or extranodal extension.
2026-08-14 | Small Intestinal Extranodal Marginal Zone Lymphoma Mimicking Crohn's Disease.
Inflammatory bowel disease (IBD) mimics pose a significant diagnostic challenge, particularly in patients with atypical features or refractory disease. Intestinal lymphomas, especially extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, can closely resemble Crohn's disease clinically, endoscopically, and histologically. We report a 23-year-old woman with a 2-year history of chronic, large-volume diarrhea, weight loss, and malabsorption, initially diagnosed and treated as Crohn's disease. Despite corticosteroids, azathioprine, and biologic therapy, she demonstrated only a partial response. Further evaluation revealed hypoalbuminemia, elevated inflammatory markers, and monoclonal gammopathy on serum protein electrophoresis. Endoscopic and radiological findings showed ileal and jejunal involvement. Histopathological examination demonstrated a dense lymphoplasmacytic infiltrate, and immunohistochemistry revealed CD20 and CD138 positivity with light chain restriction. A final diagnosis of small intestinal extranodal marginal zone lymphoma was established. The patient was treated with combined chemotherapy, with plans to escalate to rituximab-based therapy due to a suboptimal response. This case highlights the importance of reconsidering the diagnosis in patients with presumed IBD who exhibit atypical features, such as severe malabsorption, proximal small bowel involvement, monoclonal gammopathy, or refractory disease. Early recognition of IBD mimics, particularly intestinal lymphomas, is critical to ensure appropriate management and improve outcomes.
2026-07-17 | Dose-reduced (24 Gy) involved-site radiotherapy combined with rituximab in early-stage non-gastric mucosa-associated lymphoid tissue lymphoma: a prospective phase II trial.
While involved-site radiotherapy (ISRT) is the standard first-line treatment in localized non-gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the cumulative risk of distant relapse poses a persistent clinical challenge. We conducted a prospective phase II trial evaluating rituximab with 24 Gy ISRT, aiming to reduce distant relapse and enhance long-term survival. By October 2025, 60 patients with early-stage non-gastric MALT lymphoma were enrolled. Among the per-protocol efficacy-evaluable cohort (n = 55), the combined immunoradiotherapy regimen achieved a complete response rate of 100%. At a median follow-up of 30.2 months, only one distant recurrence was observed (estimated 5-year distant recurrence: 1.9%). In the full analysis set, 2- and 4-year progression-free survival rates were 98.0% and 92.9%, respectively, improving to 100% and 94.4% in the per-protocol set. Treatment-related hematologic toxicity was frequent but manageable. Infections were reported in 23.3%, including one grade 4 respiratory infection that necessitated treatment discontinuation. Immunophenotypic profiling revealed that parotid, thyroid, or mediastinal involvement correlated with higher lymphocyte proportions (39.5% ± 16.4%, P = 0.012). Post-treatment immunologic changes featured near-complete B-cell depletion and a compensatory expansion of NK cells. Overall, the combined immunoradiotherapy regimen demonstrated durable disease control in localized non-gastric MALT lymphoma, with potential synergistic benefit from NK cell-mediated immune activation. Trial registration: Chinese Clinical Trials Registry, ChiCTR2000036318; registered on Aug 22, 2020 (prospective).
2026-05-14 | Primary pulmonary mucosa-associated lymphoid tissue lymphoma with nodular pulmonary amyloidosis
82歳女性．胸部CT検査で偶然左肺S8末梢に径22 mmの空洞性結節病変を指摘された．経時的に増大傾向であり，原発性左下葉肺癌（cT1cN0M0，c-StageIA3）を疑い，診断および治療目的にロボット支援下左肺下葉切除およびリンパ節郭清（ND2a-1）を行った．腫瘤は褐色結節で病理組織学的には好酸性沈着物を認め，異物巨細胞浸潤や軽度の線維化，骨形成を伴っていた．好酸性沈着物はDFS染色陽性で過マンガン酸処理で染色性は消失せず，結節性肺アミロイドーシスの病理組織像だった．一方で辺縁は小型～中型のリンパ球や形質細胞が密に浸潤しており，免疫染色でCD20が陽性，CD43が一部陽性だった．さらに免疫グロブリン軽鎖はλ鎖優位の軽鎖制限を認め，結節性肺アミロイドーシスを合併した肺原発mucosa-associated lymphoid tissue（MALT）リンパ腫と診断した．
2026-04-09 | Treatment and outcomes of pulmonary mucosa-associated lymphoid tissue lymphoma: A multicenter analysis of 186 patients.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with pulmonary involvement is a rare, indolent lymphoma with no standard treatment approaches. To clarify patient characteristics, treatment, and prognosis of pulmonary MALT lymphoma in the modern era, a multi-institutional observational study of patients diagnosed between 2013 and 2022 was conducted. A modified Ann Arbor system was used for the analysis. Among 186 eligible patients, 131 (70%) had stage IE/IIE disease, whereas 55 (30%) had stage IV disease. No patient had stage III disease. With a median follow-up of 57 months, the 4-year overall survival (OS) rates for the stage IE, IIE, and IV groups were 96%, 92%, and 90%, respectively. The stage IIE and IV groups had similar progression-free survival (PFS) that was significantly worse than that of the stage IE group (p < .001). In stage IE/IIE patients, no differences were found in OS (p = .89) or PFS (p = .90) among the first-line treatment groups. In stage IV patients, the stomach was the most common synchronous extranodal site of involvement (36%). There were no differences in OS among the first-line treatment groups (p = .64). The OS of patients with MALT lymphoma with pulmonary involvement was favorable regardless of first-line treatment modality, including watchful waiting. The short PFS in the stage IIE and IV groups indicates that these groups are candidates for therapeutic development.
oligonucleotides
2025-10-05 | A prophylactic study of curcumin nanoparticle-induced bacterial ghosts against Helicobacter pylori in a C57BL/6 mouse model.
Gastro-duodenal diseases are becoming a chronic health burden worldwide. Helicobacter pylori plays a key role in developing gastro-duodenal disorders including dyspepsia, peptic ulcers, gastritis and MALT lymphoma. It is the major cause of stomach cancer due to infectious agents (IARC, 2020). Inefficiency of proper diagnostic approaches and reduced efficacy of existing treatments are leading to an increase in antimicrobial resistance (AMR) sharply. The development of a vaccine calls for the isolation of a potent immunogen sufficient to induce a robust immune response by activating both humoral and cellular arms of immunity. Bacterial ghost is a membrane-bound empty capsule embedded with various antigens and is an emerging next generation vaccine candidate. Curcumin, the major bioactive component of the herb turmeric, is known to have an anti-Helicobacter pylori effect, indicating its therapeutic potential as an alternative treatment. Formulation of curcumin nanoparticles alters its biophysical properties without affecting its chemical integrity, allowing the preparation of a suspension with a heterogeneous particle population. In vitro, curcumin nanoparticle-induced bacterial ghost cells (CurBGs) showed considerably reduced cytotoxicity. Serum IgG as well as its subtypes IgG1 and IgG2c were significantly evoked by three consecutive oral immunizations. Furthermore, a strong immunogen-specific response was produced in immunized animals, which may provide cross-protection regardless of the circulating H. pylori strains' cag (cytotoxin-associated gene) status. Therefore, curcumin nanoparticles treated bacterial ghosts can be an excellent novel ghost-based vaccine candidate, potentially reducing the H. pylori-mediated clinical health burden worldwide in the near future.
2025-03-13 | Targeting both death and paracaspase domains of MALT1 with antisense oligonucleotides overcomes resistance to immune-checkpoint inhibitors.
Targeting MALT1's paracaspase activity has been explored for B cell lymphoma and solid tumors. While the role of MALT1 in promoting cancer cell proliferation has been investigated, its involvement in immune evasion is unclear. Here we report that MALT1 promotes immune evasion through its paracaspase and death domain. In a paracaspase-dependent manner, MALT1 protects CD274 mRNA from degradation by its cleavage of ROQUIN1 and ROQUIN2. In a death-domain-dependent manner, MALT1 promotes the proliferation and polarization of tumor-associated macrophages to generate an immunosuppressive tumor microenvironment. Targeting MALT1 with antisense oligonucleotides inhibits PD-L1 expression in patient-derived tumor cells and suppresses the proliferation and M2-like polarization of tumor-associated macrophages isolated from patients with cancer. In preclinical models of solid tumors in female mice, treatment with MALT1 antisense oligonucleotides overcomes resistance to immune-checkpoint inhibitors. Together, our study demonstrates that targeting MALT1 is a potential strategy to overcome immune-checkpoint inhibitor resistance.
2023-05-05 | Uncovering the role of microRNA671-5p/CDCA7L/monoamine oxidase-A signaling in Helicobacter pylori mediated apoptosis in gastric epithelial cells.
Helicobacter pylori is a gram-negative microaerophilic bacterium and is associated with gastrointestinal diseases ranging from peptic ulcer and gastritis to gastric cancer and mucosa-associated lymphoid tissue lymphoma. In our laboratory, the transcriptomes and miRnomes of AGS cells infected with H. pylori have been profiled, and an miRNA-mRNA network has been constructed. MicroRNA 671-5p is upregulated during H. pylori infection of AGS cells or of mice. In this study, the role of miR-671-5p during infection has been investigated. It has been validated that miR-671-5p targets the transcriptional repressor CDCA7L, which is downregulated during infection (in vitro and in vivo) concomitant with miR-671-5p upregulation. Further, it has been established that the expression of monoamine oxidase A (MAO-A) is repressed by CDCA7L, and that MAO-A triggers the generation of reactive oxygen species (ROS). Consequently, miR-671-5p/CDCA7L signaling is linked to the generation of ROS during H. pylori infection. Finally, it has been demonstrated that ROS-mediated caspase 3 activation and apoptosis that occurs during H. pylori infection, is dependent on the miR-671-5p/CDCA7L/MAO-A axis. Based on the above reports, it is suggested that targeting miR-671-5p could offer a means of regulating the course and consequences of H. pylori infection.
2023-03-29 | Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1β, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.
2022-12-08 | Identifying tumor antigens and immune subtypes of gastrointestinal MALT lymphoma for immunotherapy development
MALT lymphoma is an extranodal B-cell lymphoma of the marginal zone of mucosa-associated lymphoid tissue (MALT), caused by malignant transformation of B-cells in the marginal zone. In this work, we aim to explore the potential relationship between MALT lymphoma and DLBCL. Vaccines derived from messenger ribonucleic acid (mRNA) may provide satisfactory results. Despite being a promising treatment option, immunotherapy isn't widely used in treating renal cell carcinoma, as only a few patients respond to the treatment. The Cancer Genome Atlas (TCGA) analysis revealed gene expression profiles and clinical information. Antigen-presenting cells infiltrated the immune system using TIMER tool (http://timer.cistrome.org/). GDSC (Genomics of Drug Sensitivity in Cancer) data were used to estimate drug sensitivity. Immune-related genes were associated with a better prognosis in MALT lymphoma patients and higher levels of antigen-presenting cells. There is a significant relationship between these immune subtypes and immunological checkpoints, immunogenic cell death regulators, and prognostic variables for MALT lymphoma patients. In this study, we provide a theoretical foundation for the development of mRNA vaccines and suggest that KLHL14 could potentially be used as antigens to develop mRNA vaccines for MALT lymphoma.
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2026-08-12 | MALT1 alternative splicing-A molecular rheostat for balancing immune activation and homeostasis.
MALT1 (mucosa-associated lymphoid tissue lymphoma/leukemia protein 1)-TRAF6 [tumor necrosis factor receptor (TNFR)-associated factor 6] interaction drives lymphocyte activation and adaptive immunity, but it also contributes to maintaining immune homeostasis. MALT1 exists in two isoforms that differ only by either encoding two (MALT1A) or one (MALT1B) TRAF6 binding motif (T6BM). The human mutation MALT1 E806D in T6BM2, expressed in both MALT1A and MALT1B, has been associated with an immune disorder combining symptoms of immune deficiency and autoimmunity. Here, we report that the orthologous germline mutation MALT1 E814D is sufficient to induce a fatal autoimmune syndrome in mice. We demonstrate that species-specific differences in the effects of T6BM2 disruptions can be attributed to alterations in MALT1 splicing and that immune homeostasis is restored by genetically enforcing expression of MALT1A in MALT1 E814D mice. Thus, alternative MALT1 splicing allows tuning of TRAF6 association, thereby functioning as a molecular rheostat to balance between optimal immune activation and maintenance of peripheral tolerance.
2025-08-01 | Loss of MALT1 Function in a Patient With Combined Immunodeficiency: a Novel Pathogenic Variant and Immunological Insights.
Germline pathogenic variants in the mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) encodes a caspase-like protease that plays a crucial role in the caspase recruitment domain (CARD)-B-cell lymphoma 10 (BCL10)-MALT1 (CBM) complex. This complex mediates the activation of nuclear factor-kB (NF-kB) pathway and are associated with diverse human diseases including combine immunodeficiency (CID), lymphoproliferation and others. This study aimed to determine the underlying cause of immune deficiency and immune dysregulation in a patient presented with recurrent respiratory infections, aphthous ulcers, dermatitis, chronic diarrhea, failure to thrive and early death. Clinical and laboratory records were reviewed. Patients underwent next-generation sequencing (NGS), and analysis of genomic DNA was performed on the patient and her parents. Lymphocyte subsets, MALT1 expression and NF-kB signaling was evaluated by flow cytometry, RT-PCR and immunoblotting. The patient carried a novel pathogenic biallelic loss-of-function variant in MALT1 (c.1411G > A; p.D471N) located in the caspase-like domain, leading to severely reduced MALT1 protein expression. Impaired CBM-mediated NF-κB activation was confirmed by reduced phosphorylation of the p65 subunit, resulting in deficient production of IL-2 and TNF-α. This functional defect caused lower Tfr and Treg cells, a normal proportion of Tfh cells, with higher expression of activation markers PD-1 and ICOS. The patient displayed low NK cell and B cell counts, together with a developmental block at the transitional B cell stage. Additionally, the proportion of marginal zone-like B cells (MZB-like) was markedly decreased, indicating impaired B cell differentiation. Human MALT1 deficiency causes profound CID by impairing CBM-mediated NF-kB signaling and MALT1-paracaspase activity. Consistent with the reported variants located in the caspase-like domain, our patient presented with an inflammatory phenotype, supporting the notion that the MALT1 D471N mutation phenocopies a partial loss of both MALT1 scaffolding function and paracaspase activity. Prompt hematopoietic stem cell transplantation (HSCT) is highly recommended as an effective therapy for MALT1 deficiency.
2025-06-01 | Marginal Zone Lymphoma: Treatment Update With a Focus on Systemic Approaches
Marginal zone lymphoma (MZL) is the second most common indolent B-cell lymphoma and comprised of three clinical subtypes based on site of involvement: extranodal marginal zone lymphoma (usually of mucosa-associated lymphoid tissue), nodal marginal zone lymphoma, and splenic marginal zone lymphoma (often with circulating villous lymphocytes). MZL is the prototype for an antigen-driven malignancy, and there are clear areas where elimination of the antigenic trigger leads to lymphoma regression. Although there is an excellent prognosis, the disease remains incurable, and the majority of patients will need repeated therapy for disease control over the course of their lifetime. Current treatment paradigms include rituximab monotherapy and chemoimmunotherapy in the frontline setting. In the relapsed or refractory setting, there are exciting advances including the recent approval of the covalent BTK inhibitor, zanubrutinib. Emerging therapies include CAR-T cell and T-cell engaging bispecific antibodies, with promising early results. This primer on MZL will discuss the three subtypes and focus on treatment approaches in the treatment-naïve and relapsed/refractory setting.
2025-03-30 | [Update on marginal zone lymphoma classification, diagnosis and treatment in 2024].
Marginal zone lymphoma (MZL) is the third most frequent lymphoma in Western countries with an increasing incidence with age. There are different histologic subtypes: Splenic MZL (SMZL), Nodal MZL (NZML), Extranodal MZL (EMZL) or MALT lymphoma and more recently, a novel entity called splenic diffuse red pulp small B-cell lymphoma. The accurate diagnosis relies on morphologic, phenotypic, cytogenetic and molecular features in order to rule out other indolent non-Hodgkin lymphomas. First line treatment depends on MZL subtypes: depending on localized or disseminated disease, MALT lymphoma are managed with radiotherapy on immunochemotherapy. SMZL, when requiring therapy, are treated with splenectomy ore more frequently monotherapy Rituximab or immunochemotherapy depending on age, comorbidities and tumor burden. Management of NMZL is often similar to Follicular lymphoma treatment. Treatment of refractory or relapsed MZL takes into account the time between the diagnosis and the progression, the nature and outcomes of previous therapies and the general condition of the patient. Conventional treatments may be a suitable option but novel therapies are more frequently used. In this review, we focus on the role of Bruton Tyrosine Kinases (where only Zanubrutinib has marketing authorization in France), PI3Kinases, Syk and BCL-2 inhibitors as well as on the results of immunomodulatory drugs and more recently the use of bispecific antibodies and T-cell chimeric antigen receptor (CAR-T cell).
2024-02-26 | Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting
Helicobacter pylori ( H. pylori ) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori , underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections.
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Drug Discovery Landscape
11 orphan drug designations for MALT lymphoma, including 5 approved therapies.
11 orphan drug designations for MALT lymphoma, including 5 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
odronextamab | antibodies | FDA | Regeneron Pharmaceuticals, Inc. | |
lisocabtagene maraleucel [Breyanzi] | cell therapies | FDA | Approved | Juno Therapeutics, Inc., a Bristol-Myers Squibb Company |
zanubrutinib [Brukinsa] | small molecules | FDA | Approved | BeOne Medicines USA, Inc. |
axicabtagene ciloleucel | cell therapies | FDA | Kite Pharma, Inc. | |
parsaclisib | small molecules | FDA | Incyte Corporation | |
umbralisib [Ukoniq] | small molecules | FDA | Approved | TG Therapeutics, Inc. |
copanlisib | small molecules | FDA | Bayer HealthCare Pharmaceuticals, Inc. | |
ibrutinib [Imbruvica] | small molecules | FDA | Approved | Pharmacyclics, LLC |
lenalidomide [Revlimid] | small molecules | FDA | Approved | Celgene Corporation |
idelalisib | small molecules | FDA | Gilead Sciences, Inc. | |
ublituximab | antibodies | FDA | TG Therapeutics, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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