Enhancement of CAR-T cell efficacy and persistence via CD30 costimulation and NF-κB signaling.

ABSTRACT: Although chimeric antigen receptor (CAR)-redirected T lymphocytes have achieved unprecedented clinical responses in hematologic neoplasms, their role in solid tumors still needs to be improved. To overcome current limitations, we rationally designed a next-generation CAR-T cell construct incorporating autonomous costimulatory signaling pathways that operate independently of tumor antigen engagement, thus faithfully emulating physiological T cell activation paradigms. We screened seven costimulatory receptors from the TNF receptor superfamily and identified that CD30 is the most effective enhancer of CAR-T cell function. Subsequent structural analysis revealed that the intracellular domain (ICD) of CD30 is primarily responsible for its costimulatory activity. Our data showed that these CAR-

SUBMITTER: Su Y 

PROVIDER: S-EPMC12613410 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature