Enhanced cytotoxicity against cholangiocarcinoma by fifth-generation chimeric antigen receptor T cells targeting integrin αvβ6 and secreting anti-PD-L1 scFv.

ABSTRACT: Cholangiocarcinoma (CCA) is a fatal bile duct cancer with high resistance and recurrence rates, with only one fifth of patients eligible for surgical treatment. The disease resists standard chemotherapy and often relapses. Chimeric antigen receptor (CAR) T cell therapy has shown promise for hematological malignancies but faces challenges in solid tumors due to resistance mechanisms like PD-L1 expression, which tumors use to evade the immune system. To address this challenge, we developed fifth-generation CAR T cells targeting integrin αvβ6 that also secrete anti-PD-L1 single-chain variable fragment (scFv) to target both tumor cells and the PD-1/PD-L1 pathway. We examined integrin αvβ6 and PD-L1 expression in CCA cell lines and engineered T cells to express either fourth-generation CAR T ce

SUBMITTER: Phanthaphol N 

PROVIDER: S-EPMC12004729 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature