Sensitizing solid tumors to CAR-mediated cytotoxicity by lipid nanoparticle delivery of synthetic antigens.

ABSTRACT: Chimeric antigen receptor (CAR) T cell immunotherapy relies on CAR targeting of tumor-associated antigens; however, heterogenous antigen expression, interpatient variation and off-tumor expression by healthy cells remain barriers. Here we develop synthetic antigens to sensitize solid tumors for recognition and elimination by CAR T cells. Unlike tumor-associated antigens, we design synthetic antigens that are orthogonal to endogenous proteins to eliminate off-tumor targeting and that have a small genetic footprint to facilitate efficient tumor delivery to tumors by lipid nanoparticles. Using a camelid single-domain antibody (VHH) as a synthetic antigen, we show that adoptive transfer of anti-VHH CAR T cells to female mice bearing VHH-expressing tumors reduced tumor burden in multiple syngen

SUBMITTER: Gamboa L 

PROVIDER: S-EPMC12305469 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature