2026-07-09 | Clinical analysis and follow up study of chronic granulomatous disease with neonatal onset

Objective To address the existing gap in knowledge regarding the small subset of chronic granulomatous disease (CGD) patients who present during the neonatal period, this study aimed to characterize their clinical features, genetic profiles, and long-term prognosis. Methods This study retrospectively selected CGD patients with neonatal onset who were diagnosed using neutrophil respiratory burst tests and genetic analysis at the Guangzhou Women and Children's Medical Center, Guangzhou Medical University, between January 2018 and September 2024. Results This study included nine male patients diagnosed with CGD presenting with neonatal onset. The median age at onset was 20 days (7–23 days). Pneumonia was observed in eight patients (88.9%), with Aspergillus species detected in five of these cases (62.5%). The stimulation index (SI) in the neutrophil oxidative burst assay was significantly reduced. All nine patients exhibited hemizygous variants in the CYBB gene. The median hospital stay was 42 days (15.5–48 days). Three patients died due to disease progression during their initial hospitalization. Regarding long-term prognosis, one patient was lost to follow-up at six months of age, and three patients died from severe infections during infancy. The remaining two patients underwent hematopoietic stem cell transplantation (HSCT) and achieved complete clinical remission. Conclusion Patients with CGD presenting in the neonatal period predominantly harbor mutations in the CYBB gene, which are associated with severe clinical manifestations. Aspergillus species are the most common pathogens in these patients. Although the prognosis is generally poor, it may be improved by hematopoietic stem cell transplantation (HSCT).

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2026-06-25 | Thalidomide for CGD-related inflammatory bowel disease: A randomized, double-blind trial.

Chronic granulomatous disease-related inflammatory bowel disease (CGD-IBD) requires effective and safe therapies, as conventional immunosuppressants increase infection risk. Thalidomide, with anti-inflammatory and immunomodulatory effects, may represent a therapeutic option. This study was conducted to explore the preliminary efficacy and safety of thalidomide for CGD-IBD in a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II trial. Patients were randomized to thalidomide or placebo for a 12-wk blinded phase, followed by a 12-wk extension thalidomide phase. The primary endpoint was achievement of remission or a ≥20-point reduction in the Pediatric Ulcerative Colitis Activity Index. Eight male patients were randomized and analyzed. The primary endpoint was achieved by 1/3 of thalidomide patients versus 0/5 in the placebo group during the blinded phase, and by 5/8 in the extension phase. Secondary endpoints and exploratory endoscopy showed improvements. CGD-related infection rates were comparable before and after treatment. Thalidomide met the prespecified efficacy criterion with an acceptable safety profile in CGD-IBD, suggesting a promising therapeutic option that warrants further clinical studies.

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2026-06-20 | Expansion and CAR engineering of granulocyte-monocyte progenitors for cellular immunotherapy.

Engineered macrophages are promising for tumor immunotherapy but are limited by poor ex vivo expansion, genetic tractability, and biodistribution after transfer. Here, we develop defined culture conditions that enable long-term expansion of mouse and human granulocyte-monocyte progenitors (GMPs) while preserving progenitor identity and myeloid potential, establishing GMPs as a renewable engineering platform. Mechanistically, we identify myeloperoxidase as a regulator of GMP proliferation. Expanded GMPs are readily engineered and, after transfer, seed hematopoietic niches and generate donor-derived myelopoiesis that restores antibacterial defense in chronic granulomatous disease mice and yields abundant tumor-infiltrating macrophages. GMPs engineered with chimeric antigen receptors (CARs) suppress CD19-positive leukemia and human epidermal growth factor receptor 2 (HER2)-positive solid tumors. We further introduce a CAR incorporating an immunoglobulin G (IgG) Fc domain that recruits host Fc receptor-expressing phagocytes, enables T cell priming across major histocompatibility complex (MHC) mismatch, and enhances efficacy in immunocompetent allogeneic cancer models. Together, these findings establish expandable GMPs as a scalable platform for engineered immunotherapy.

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