Dual targeting of solid tumors using cytokine-induced killer cells modified with a CAR anti-tenascin C and a secretable EGFRxCD3 bispecific antibody.

ABSTRACT: To generate CARCIK cells with enhanced targeting and penetration of solid tumors, we have designed new CAR molecules against tenascin C (TNC), an extracellular matrix and surface molecule, overexpressed in several tumor types. Two different anti-TNC CAR constructs were generated, sharing the anti-TNC scFv domain, fused to the CD3ζ fragment, but differing in co-signaling domains: CAR-TNC4 carrying the 4-1BB and CAR-TNC5 the CD28 and OX40 domains. Both CARs were introduced into cytokine-induced killer cells (CIK) by co-transfection with the sleeping beauty transposase plasmid. CARCIK-TNC cells were cytotoxic against TNC⁺ targets, proliferated and secreted the IFN-γ and IL-2 cytokines in response to target cell binding, with overall higher efficacy of CARCIK-TNC5 compared to CARCIK

SUBMITTER: Zaninelli S 

PROVIDER: S-EPMC12433391 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature