Senescence-targeted engineered CAR-T immunotherapy: advances, challenges and perspectives for engineered senolytic immunotherapy.
Abstract
Cellular senescence acts as a core driver of chronic diseases and tissue degeneration. Conventional small-molecule senolytics face critical limitations including poor target specificity and off-target toxicity when eliminating heterogeneous senescent cell populations. This review systematically discusses senescence-targeted engineered chimeric antigen receptor (CAR)-T immunotherapy, which achieves targeted clearance of pathological senescent cells by recognising specific surface markers. It summarises target-antigen evaluation frameworks, analyzes aged immunosuppressive microenvironment barriers and corresponding engineering strategies, and outlines composite efficacy assessment systems and tiered biomarker-monitoring workflows. Key translational bottlenecks such as imperfect antigen specificity and immune escape are also addressed. Preclinical studies verify organ function restoration and healthspan extension, while clinical evidence remains limited. Future integration of CAR-T technology with smart nanocarriers, synthetic biology and artificial intelligence will promote its clinical translation for senescence-associated disorders.
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Research summary
This review evaluates the potential of engineered CAR-T cells to target and eliminate senescent cells, a core driver of aging, as an alternative to small-molecule senolytics. The paper is relevant because it addresses the root cause of aging (cellular senescence) by proposing a novel immunotherapeutic mechanism to clear senescent cells, although it is a review of preclinical advances rather than a primary breakthrough study.
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