肿瘤细胞治疗研究
英文原题：Chimeric antigen receptor-T cell therapy for T cell-derived hematological malignancies.
复发/难治性 T 细胞来源恶性肿瘤具有高度异质性和不良预后。
复发/难治性T细胞来源恶性肿瘤具有高度异质性，预后较差。近期，嵌合抗原受体（CAR）T细胞疗法治疗B细胞来源恶性肿瘤取得了显著疗效且安全性良好。然而，由于正常T细胞与恶性T细胞相似，CAR-T疗法治疗T细胞来源恶性肿瘤受到更多限制，例如自相残杀、T细胞再生障碍和肿瘤污染。临床试验中应用最广泛的泛T细胞抗原CAR-T细胞（如靶向CD5和CD7）几乎可以覆盖所有T细胞来源的恶性细胞，但也会严重杀伤CAR-T细胞及正常T细胞。与自体CAR-T细胞相比，异基因CAR-T细胞可避免肿瘤污染，并通过基因编辑制成通用型产品。不过，目前这些CAR-T细胞均无法完全避免靶向T细胞CAR-T治疗后免疫缺陷及疾病复发。本综述总结CAR-T细胞治疗T细胞来源恶性肿瘤在临床实践中的现有挑战，并讨论解决这些局限的潜在策略。
Relapsed/refractory T cell-derived malignancies present with high heterogeneity and poor prognoses. Recently, chimeric antigen receptor (CAR)-T cell therapy has shown remarkable safety and efficacy in the treatment of B cell-derived malignancies. However, the treatment of CAR-T cells in T cell-derived malignancies has more limitations, such as fratricide, T cell aplasia, and tumor contamination, mainly because of the similarity between normal and malignant T cells. Pan-T antigen CAR-T cells (such as CD5 and CD7 targets), the most widely used CAR-T cells in clinical trials, can cover almost all T cell-derived malignant cells but can also induce severe killing of CAR-T cells and normal T cells. Compared to autologous sources of CAR-T cells, allogeneic CAR-T cells can prevent tumor contamination and become universal products by gene-editing. However, none of these CAR-T cells could completely prevent immune deficiency and disease relapse after T-targeted CAR-T cell therapy. In this review, we summarize the current challenges of CAR-T cell therapy for T cell-derived malignancies in clinical practice and potential strategies to address these limitations.
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