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New Development in CAR-T Cell Therapy


New Development in CAR-T Cell Therapy

Zhenguang Wang et al. J Hematol Oncol.


Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have yielded unprecedented efficacy in B cell malignancies, most remarkably in anti-CD19 CAR-T cells for B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate. However, tumor antigen escape has emerged as a main challenge for the long-term disease control of this promising immunotherapy in B cell malignancies. In addition, this success has encountered significant hurdles in translation to solid tumors, and the safety of the on-target/off-tumor recognition of normal tissues is one of the main reasons. In this mini-review, we characterize some of the mechanisms for antigen loss relapse and new strategies to address this issue. In addition, we discuss some novel CAR designs that are being considered to enhance the safety of CAR-T cell therapy in solid tumors.

Keywords: Adoptive cell therapy; CAR-T; Cancer treatment; Chimeric antigen receptor; Engineered T cells.


Fig. 1
Fig. 1
Future directions in CAR-T cell therapy. Overcoming antigen loss relapse and enhancing efficacy and safety present a principal direction of CAR-T cell therapy optimization. “Off-the-shelf” CAR-T, a biologic that is pre-prepared in advance from one or more healthy unrelated donors, validated, and cryopreserved and then can be shipped to patients worldwide, is deemed to be the ultimate product formulation. CAR chimeric antigen receptor, CAR-T cell chimeric antigen receptor-modified T cell, B-ALL B cell acute lymphoblastic leukemia, B-NHL B cell non-Hodgkin’s lymphoma, CLL chronic lymphocytic leukemia, HL Hodgkin’s lymphoma, MM multiple myeloma, EGFR epidermal growth factor receptor, MSLN mesothelin, HER2 human epidermal growth factor receptor-2, EGFRvIII variant III of the epidermal growth factor receptor, PSMA prostate-specific membrane antigen, CEA carcinoembryonic antigen

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