Zheng Haiqiong, Zhao Houli, Han Shi, Kong Delin, Zhang Qiqi, Zhang Mingming, Chen Yijin, Zhang Meng, Hu Yongxian, Huang He
Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Hematology, Zhejiang University, Hangzhou, China.
Exp Hematol Oncol. 2024 Nov 28;13(1):117. doi: 10.1186/s40164-024-00584-6.
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.
复发/难治性T细胞来源的恶性肿瘤具有高度异质性且预后较差。最近，嵌合抗原受体（CAR）T细胞疗法在治疗B细胞来源的恶性肿瘤方面显示出显著的安全性和有效性。然而，CAR-T细胞在T细胞来源的恶性肿瘤治疗中存在更多限制，如自相残杀、T细胞发育不全和肿瘤污染，主要是因为正常T细胞和恶性T细胞之间存在相似性。泛T抗原CAR-T细胞（如CD5和CD7靶点）是临床试验中使用最广泛的CAR-T细胞，几乎可以覆盖所有T细胞来源的恶性细胞，但也会诱导CAR-T细胞和正常T细胞的严重杀伤。与自体来源的CAR-T细胞相比，同种异体CAR-T细胞可以通过基因编辑防止肿瘤污染并成为通用产品。然而，这些CAR-T细胞都无法完全预防T靶向CAR-T细胞治疗后的免疫缺陷和疾病复发。在这篇综述中，我们总结了CAR-T细胞疗法在临床实践中治疗T细胞来源的恶性肿瘤时面临的当前挑战以及解决这些限制的潜在策略。
