IPSC-derived trimodal T cells engineered with CAR, TCR, and hnCD16 modalities can overcome antigen escape in heterogeneous tumors.

ABSTRACT: Although chimeric antigen receptor (CAR) T cells have demonstrated therapeutic activity in hematopoietic malignancies, tumor heterogeneity has impeded the efficacy of CAR T cells and their extension into successful solid tumor treatment. To address these challenges, induced pluripotent stem cell (iPSC)-derived T (iT) cells are engineered to uniformly express CAR and T cell receptor (TCR), enabling targeting of both surface and intracellular antigens, respectively, along with a high-affinity, non-cleavable variant of CD16a (hnCD16) to support antibody-dependent cellular cytotoxicity (ADCC) when combined with therapeutic antibodies. Co-expression of each antitumor strategy on engineered iT cells enables independent and antigen-specific targeting across a diverse set of liquid and solid tumor

SUBMITTER: Yang BH 

PROVIDER: S-EPMC12281410 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature