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 fatal malignancy with an increasing prevalence, a high mortality rate, poor overall survival, and limited responsiveness to conventional chemoradiotherapy. 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 of immunotherapeutic approaches including 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 cholangiocarcinoma remains largely unexplored. This article offers an overview of the current landscape of antibody-based immunotherapy, particularly CAR-T therapy and vaccines in the context of cholangiocarcinoma 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.