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TIGIT and PVRIG are immune checkpoints co-expressed on activated T and NK cells, contributing to tumor immune evasion. Simultaneous blockade of these pathways may enhance therapeutic efficacy, positioning them as promising dual targets for cancer immunotherapy. This study aimed to develop a bispecific antibody (BsAb) to co-target TIGIT and PVRIG.
View Article and Find Full Text PDFMalaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.
PLoS Pathog
January 2025
Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland, United States of America.
Malaria is a complex parasitic disease caused by species of Plasmodium parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement.
View Article and Find Full Text PDFMicroenvironment-confined kinetic elucidation and implementation of a DNA nano-phage with a shielded internal computing layer.
Nat Commun
January 2025
Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Multiple receptor analysis-based DNA molecular computation has been developed to mitigate the off-target effect caused by nonspecific expression of cell membrane receptors. However, it is quite difficult to involve nanobodies into molecular computation with programmed recognition order because of the "always-on" response mode and the inconvenient molecular programming. Here we propose a spatial segregation-based molecular computing strategy with a shielded internal computing layer termed DNA nano-phage (DNP) to program nanobody into DNA molecular computation and build a series of kinetic models to elucidate the mechanism of microenvironment-confinement.
View Article and Find Full Text PDFTriple knockdown of , , and in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice.
Sci Transl Med
January 2025
Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue.
View Article and Find Full Text PDFBivalent OX40 Aptamer and CpG as Dual Agonists for Cancer Immunotherapy.
ACS Appl Mater Interfaces
January 2025
College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
Cancer immunotherapy has revolutionized cancer treatment by harnessing the body's immune system to recognize and attack tumors. Over the past 25 years, the use of blocking antibodies has fundamentally transformed the landscape of cancer therapy. However, despite extensive research, agonist antibodies targeting costimulatory receptors such as ICOS, GITR, OX40, CD27, and 4-1BB have consistently underperformed in clinical trials over the past 15 years, failing to meet the anticipated success.
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