Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

Abstract Chimeric Antigen Receptor T‐cell (CAR‐T cell) therapy has emerged as a groundbreaking immunotherapeutic approach for treating various hematological malignancies. CAR‐T cells are engineered to express synthetic receptors that target specific antigens on cancer cells, leading to their eradication. While the therapy has shown remarkable efficacy, a significant challenge that has been observed in 30%–70% of patients showing recurrent disease is antigen loss or downregulation. We searched PubMed/MEDLINE, EMBASE, and Google scholar for articles on antigen loss/escape following Chimeric antigen receptor T‐cell therapy in malignancies. Antigen loss refers to the loss or reduction in the expression of the target antigen on cancer cells, rendering CAR‐T cells ineffective. This phenomenon poses a significant clinical concern, as it can lead to disease relapse and limited treatment options. This review explores the mechanisms underlying antigen loss following CAR‐T cell therapy, its implications on treatment outcomes, and potential strategies to overcome the problem.