抑制衰老的 p53 异构体 Δ133p53α：增强肿瘤免疫治疗并探索衰老相关疾病的新型治疗策略

133p53 is a naturally occurring isoform of the tumor suppressor protein p53. 133p53 functions as a physiological dominant-negative inhibitor of the full-length p53 protein (commonly referred to as p53). 133p53 preferentially inhibits p53-mediated cellular senescence, while it does not inhibit, or may even promote, p53-mediated DNA repair. Owing to this selective inhibitory activity that preserves genome stability, 133p53 represents a promising target for enhancement in the prevention and treatment of diseases associated with increased senescence of normal cells. These diseases include Alzheimer's and other neurodegenerative diseases, premature aging diseases such as Hutchinson-Gilford progeria syndrome (HGPS), and idiopathic pulmonary fibrosis (IPF).

Current cell-based therapies, which are limited by increased cellular senescence, may also benefit from 133p53 -mediated improvements. As an initial application of 133p53 in improving therapeutic cells, we here introduce 133p53 -armored chimeric antigen receptor (CAR)-T cells.

Based on our previous and ongoing studies using various types of senescent human cells in vitro, we also discuss the importance of further exploring the therapeutic potentials of 133p53 , with particular focus on HGPS and IPF. The development of mouse models facilitates in vivo evaluation of the therapeutic effects of 133p53 , potentially leading to future clinical applications.