Relapse Mechanism and Treatment Strategy After Chimeric Antigen Receptor T-Cell Therapy in Treating B-Cell Hematological Malignancies

Abstract

Over the past few decades, immunotherapy has revolutionized the modern medical oncology field. Chimeric antigen receptor (CAR)-T cell therapy has a promising curative effect in the treatment of hematological malignancies. Anti-CD19 CAR-T cells are the most mature CAR-T cells recently studied and in recent years it has achieved a complete remission rate of approximately 90% in the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Although CAR-T cell therapy has greatly alleviated the disease in patients with leukemia or lymphoma, some of them still relapse after treatment. Therefore, in this article, we discuss the factors that may contribute to disease relapse following CAR-T cell therapy and summarize potential strategies to overcome these obstacles, thus providing the possibility of improving standard treatment regimens.

Combination of CAR‑T cell therapy and radiotherapy: Opportunities and challenges in solid tumors (Review)

“…During follow-up of a clinical trial on the treatment of recurrent and/or refractory acute lymphocytic leukemia with CD19 targeted CAR-T cells, CD19 antigen was reported to be downregulated in tumor cells, which led to therapy resistance (23,24). Although CAR-T cells targeting a single antigen have shown good anti-tumor efficacy in the early stage of hematological malignancies, the recurrence rate is high due to the tumor cells partially or completely losing the expression of target antigen in the late stages (15,25). However, the mechanism of antigen escape is still unclear.…”

Bicistronic CAR-T cells targeting CD123 and CLL1 for AML to reduce the risk of antigen escape

“…Another challenge with CAR-T therapy is antigen-negative relapse. Several patients who received anti-CD19 CAR-T cells have had a relapse of their illness with loss of CD19 expression [ 12 , 13 ]. Hence, targeting multiple antigens simultaneously is one tactic to combat target antigen loss following CAR-T therapy.…”