2026-08-06 | Next-generation T cell engagers for cancer and autoimmune diseases.
T cell-engaging antibody constructs (TCEs) have emerged as a potent modality to treat cancer and autoimmune diseases. Twelve TCEs have been approved by the FDA and EMA for the treatment of hematological malignancies or solid tumors. Despite the varying designs and binding properties, they all lead to robust single-agent efficacy and approvals in refractory or relapsed leukemia, lymphomas, multiple myeloma (MM), small cell lung cancer, EpCAM-expressing cancers or uveal melanoma. Where comparisons can be deduced, TCEs appear to achieve response rates like those obtained with CAR-T cell therapies. Given the success of the first generation of TCEs, considerable attempts are underway to further improve upon this modality. With the goal of expanding TCEs into other malignant and autoimmune indications, and to further enhance efficacy and improve safety, a multitude of novel TCEs are currently in preclinical and clinical development. Here we review the current approaches to developing next-generation TCEs that can widen the therapeutic index, address heterogeneous target expression, and thereby potentially improve efficacy and safety.
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2026-08-05 | Identification and Validation of an E2F Targets-Related Gene Signature Risk Score Predicting the Prognosis of Patients with Uveal Melanoma.
Uveal melanoma (UM) is a challenging malignancy, in terms of diagnosis, risk stratification, and treatment associated with high morbidity and mortality rates. It has been demonstrated that E2F-related pathways play a significant role in the tumorigenesis and distant metastasis of UM. In this study, the E2F target-related genes were utilized to construct and validate a prognostic risk score for patients with UM. Using the TCGA-UVM cohort (n = 80), 192 E2F target genes were screened using gene set enrichment analysis (GSEA) to identify survival-associated genes. Prognostic genes were filtered using Kaplan-Meier analysis, univariate Cox regression, and LASSO, followed by multivariate Cox regression to construct a risk score model. The model was validated using the GSE22138 cohort (n = 63). Functional annotations of the risk score and its impact on stratifying tumor immune microenvironment components were assessed. A total of 9 genes (CDC25B, NME1, RFC2, PRDX4, NASP, UBE2S, PRKDC, MCM6, and LBR) passed the model construction pipeline. The risk score categorization system showed an independent prognostic power (HR: 2.34, 95% CI: 1.11-4.90, p = 0.025) and a good predictability of the survival outcome (receiver operating characteristic curve analysis: area under the curve = 0.730, 95% CI: 0.60-0.86, p = 0.002). When analyzing the most frequently mutated gene cohorts, the risk score was significantly lower in the mutated subgroups of GNAQ, SF3B1, and EIF1AX. In contrast, the risk score was notably higher in the BAP1 mutated subgroup. Copy number analysis of chromosomal arms showed significant correlations between the risk score and 1q, 3q, 3p, 6p, 8q. The high-risk group showed significant infiltration for NK cells, plasma B cells, gamma delta T cells, follicular T cells, M1 and M2 macrophages with lower infiltration of common myeloid progenitor cells. In addition, the high-risk group showed higher immune and microenvironment scores. The developed E2F target-related gene model offers a robust tool for predicting the prognosis of UM patients. As a potential risk stratification method for UM, this model could have clinical applications pending further evaluation.
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2026-08-05 | Percutaneous Hepatic Perfusion: Continuum of Nursing Care and Safety Implications for Managing Patients With Metastatic Uveal Melanoma.
Uveal melanoma is a rare cancer that can metastasize to the liver. Percutaneous hepatic perfusion (PHP) is a minimally invasive technique that delivers melphalan directly to the liver to treat metastatic uveal melanoma. This article presents nursing care and safety recommendations across all phases of the PHP procedure for patients with metastatic uveal melanoma. A multidisciplinary team of subject matter expert nurses, along with a clinic-based physician assistant, reviewed current literature, clinical guidelines, and trial protocols. The team identified best practices for nursing care during clinic visits, preprocedure preparation, intraprocedure monitoring, hazardous drug safe handling, postprocedure care, critical care and recovery, and follow-up. Collaborative nursing care across specialties is essential for the safe and effective delivery of melphalan via PHP. These recommendations provide guidance on patient assessment, monitoring, management of adverse events, and patient education. As PHP becomes more widely used nationally, nurses unfamiliar with this specialized procedure will benefit from structured, evidence-informed care protocols.
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2026-07-29 | Radiation retinopathy: a review.
Radiation retinopathy (RR) and radiation maculopathy (RM) are common, vision-threatening complications of ocular and periocular radiotherapy, particularly after treatment of uveal melanoma. They result from progressive occlusive microangiopathy leading to retinal ischemia, macular edema, and visual decline. With the increasing use of plaque brachytherapy and proton beam therapy, understanding their epidemiology, risk factors, and management is essential to improve outcomes. RR and RM arise from radiation-induced endothelial and pericyte injury causing blood-retinal barrier breakdown, ischemia, and neuronal loss. Risk is influenced by patient factors (diabetes, hypertension, chemotherapy), tumor characteristics (size, location), and radiation parameters (dose, isotope, fractionation). Advances in imaging, especially OCT and OCT angiography, permit early detection of subclinical edema and microvascular ischemia before funduscopic changes. Classification systems integrating fundus, angiographic, and OCT features provide standardized grading. Treatment remains challenging, though anti-VEGF agents (bevacizumab, ranibizumab, aflibercept) demonstrate the strongest evidence for reducing edema, stabilizing anatomy, and preserving vision; however, no treatment has demonstrated clear superiority, and outcomes are largely derived from non-comparative studies. Early and sustained therapy yields better outcomes, though recurrence is common. Emerging agents such as faricimab are under investigation. RR and RM remain major obstacles to long-term visual preservation after ocular radiotherapy. Multimodal imaging enables earlier diagnosis, while anti-VEGF therapy is the current standard of care. Clinicians should maintain vigilance in at-risk patients, initiate timely treatment, and use imaging biomarkers to guide follow-up. Future research should optimize treatment regimens and evaluate novel therapeutics to further improve visual outcomes.
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2026-07-27 | Uveal melanoma as a stress-dependent malignancy governed by a reprogrammable stress-adaptation network.
Uveal melanoma (UM) is a biologically distinct intraocular malignancy with a strong tendency for hepatic metastasis and limited responsiveness to current systemic therapies. Emerging evidence suggests that UM progression is sustained by interconnected stress-response pathways rather than by oncogenic signaling alone. In this Review, we propose that UM is best understood as a stress-dependent malignancy in which GNAQ/GNA11 mutations, BAP1 loss, and sequential ocular-to-hepatic microenvironmental pressures converge on a reprogrammable stress-adaptation network. This network links hypoxia signaling, metabolic plasticity, redox control, proteostasis, and autophagy/mitophagy to metastatic fitness, immune escape, and treatment resistance. We further highlight oxidative stress as a central vulnerability, with moderate reactive oxygen species supporting tumor adaptation whereas excessive ROS may trigger mitochondrial dysfunction, YAP suppression, ferroptosis, and immunogenic cell death. By integrating molecular, metabolic, and ecological perspectives, this framework extends prior UM reviews by identifying stress adaptation as a central organizing principle of UM biology and a source of actionable therapeutic liabilities, including redox regulation, UPR/ISR signaling, mitophagy dependence, and ferroptosis sensitivity.
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