Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.

Cholangiocarcinoma (CCA) is a highly lethal malignancy with rising incidence, high mortality, poor overall survival rates, and limited responsiveness to traditional chemo-radiotherapy. Targeted therapies addressing specific gene mutations have expanded treatment options for some patient populations. The introduction of chimeric antigen receptor-modified T cell (CAR-T) immunotherapy and personalized vaccines have opened up a new avenue for managing various cancers. Considerable efforts have been dedicated to preclinical research and ongoing clinical trials aimed at investigating immunotherapeutic approaches such as CAR-T therapy, vaccines, and antibody-based therapies such as antibody drug conjugates. However, the potential of CAR-T therapy and vaccines in treating advanced unresectable/metastatic CCA remains largely unexplored. This review offers an overview of the current landscape of antibody-based immunotherapy, particularly CAR-T therapy and vaccines in the context of CCA treatment. It outlines a framework for selecting CAR-T and vaccine targets and delves into the biology of promising targetable antigens, as well as potential future therapeutic targets.