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Opportunities and challenges of CAR-T cell for tumor therapy
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Abstract:
Currently, chimeric antigen receptor gene-modified T（CAR-T）cell as a viable medicine has achieved exciting efficacy in therapies of blood cancers, which has been widely recognized as a new direction of tumor treatment by the medical community. Throughout the development course of cellular immunotherapy technology, any novel therapy approach needs a continuous improvement process from laboratory to clinical application, does as the CAR-T cell therapy technique. Although it showed unprecedented efficacy in the therapy for hematologic malignancies: the CR rate of advanced recurent relapsed refractory acute lymphoblastic leukemia (ALL) can reach 90%, and the CR rate of chronic lymphocytic leukemia (CLL) and partial B-cell lymphoma can also reach more than 50%, some problems still exsist in the course of treating hematologic malignancies with the CAR-T, such as off-target effect, toxic side effects, short duration of in vivo, high rate of recurrence and so on. It has been conformed that treatment of solid tumors with the CAR-T is safe and effective, but its efficacy remains to be improved. In view of the above problems, the author summarizes six strategies to improve the therapeutic efficacy of the CAR-T: (1) Overcoming defects of T cells in the patients; (2) Selecting optimal culture conditions for the CAR-T cell; (3) Instituting Optimal program of target cell stimulation; (4) Confirming approach of pre-condition by chemotherapy; (5) Achieving the humanized CAR; (6) Enhancing combination of co-stimulatory signals.This article reviewed recent progresses of the CAR-T cytotherapy technique and urgently solved problems in this field.
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Project Supported:
Project supported by the National Key R&D Program of China (No.2016YFC1303400), and the National Natural Science Foundation of China (No.81520108025, No.81330048)
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