[CAR T-cell therapy for T cell malignancies: challenges and recent advances].

细胞疗法 医学 细胞 生物 遗传学
作者
Haruko Tashiro
出处
期刊:PubMed [National Institutes of Health]
卷期号:65 (7): 644-651
标识
DOI:10.11406/rinketsu.65.644
摘要

T cell malignancies pose several unique issues for CAR-T cell therapy that were not significant concerns with CAR-T cells for B-cell malignancies. A general problem to consider in the production of CAR-T cells is "on target-off tumor toxicity." This occurs when the antigen targeted by the CAR-T cells is also expressed on normal cells, not just tumor cells, which causes CAR-T cells to damage these normal cells. In CAR-T cell therapy for T cell tumors, antigens expressed on T cells (such as CD5, CD7, etc.) are the targets, which leads to a problem known as "fratricide," where CAR-T cells kill each other. Other issues include T cell aplasia and contamination of CAR-T cell products with tumor cells. However, several recent clinical trials have shown excellent outcomes for CAR-T cell therapy when genome editing technology is used to overcome these issues by knocking out target antigens or T cell receptors. This review article outlines these challenges and their solutions and discusses the results of recent clinical trials.

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