Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors.

ABSTRACT: Although natural killer (NK) cells are endowed with intrinsic cytotoxicity, their therapeutic application often faces limitations because of their lack of tumor-specific targeting ability and limited ability to infiltrate solid tumors. To overcome these limitations, we developed anti-mesothelin (MSLN) uCAR-like NK cells, which are designed to enhance both the targeting specificity and tumor infiltration capacity, thereby improving the antitumor efficacy of NK cell-based therapies. We constructed, purified, and validated a tetravalent bispecific cell engager (MSLN×CD16A) via the SpyTag/SpyCatcher system. Cytokine-induced memory-like NK cells, induced by IL-12, IL-15, and IL-18, were precomplexed with MSLN×CD16A to generate anti-MSLN CAR-like NK cells. To further enhance tumor penetration, t

SUBMITTER: An M 

PROVIDER: S-EPMC12727736 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature