Nicotinamide Riboside Hydrogel Enhances T Cell Therapy: Preclinical Findings

Synopsis

T cell-based immunotherapy (TCBI) is a promising cancer treatment, but its success is often limited by weak immune activation, T cell exhaustion, and tumor immune evasion through the PD-1/PD-L1 pathway. This study developed a novel injectable hydrogel made from chemically modified tumor lysates, which acts as both a vaccine and a drug delivery system. The hydrogel provides a long-lasting source of tumor antigens to strengthen immune recognition, while encapsulating nicotinamide riboside (NR) and SB415286—two compounds that enhance mitochondrial quality (via mitophagy) in T cells and suppress PD-1 expression, preventing immune fatigue. When injected into tumors, the hydrogel created a powerful immune microenvironment, significantly boosting T cell activity and antitumor effects. This approach represents a new way to rejuvenate and reprogram the body’s own T cells directly within tumors, offering a major advance in personalized cancer immunotherapy.

Journal

Journal of Controlled Release