肿瘤细胞治疗研究
英文原题：Novel and multiple targets for chimeric antigen receptor-based therapies in lymphoma.
Novel and multiple targets for chimeric antigen receptor-based therapies in lymphoma.
靶向 CD19 的嵌合抗原受体（CAR）T 细胞疗法在 B 细胞非霍奇金淋巴瘤（NHL）中的应用，验证了基于 CAR 的疗法对淋巴系统恶性肿瘤的价值。
靶向 CD19 的嵌合抗原受体（CAR）T 细胞治疗 B 细胞非霍奇金淋巴瘤（NHL）的成功验证了 CAR 疗法用于淋巴瘤恶性肿瘤的价值。尽管疗效显著，CD19 抗原丢失、突变或下调导致治疗失败，仍是治愈的主要障碍。CD19-CAR-T 的“靶向肿瘤但同时损伤正常组织”效应可造成长期 B 细胞缺乏等副作用，限制了其在慢性淋巴细胞白血病（CLL）等惰性疾病中的应用。替代 CAR 靶点及多特异性 CAR 可能改善 B 细胞非霍奇金淋巴瘤（B-NHL）的细胞疗法结局。针对霍奇金淋巴瘤和 T 细胞淋巴瘤，已有多个细胞表面抗原被研究作为 CAR 靶点，部分已在临床试验中显示良好前景。有些抗原由不同类型淋巴瘤表达，可用于设计不依赖特定肿瘤类型的 CAR。本文综述用于新型 CAR 疗法的已研究抗原，以及用于治疗淋巴瘤、同时靶向两个或更多抗原的 CAR 设计。
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 in B-cell non-Hodgkin lymphoma (NHL) validates the utility of CAR-based therapy for lymphomatous malignancies. Despite the success, treatment failure due to CD19 antigen loss, mutation, or down-regulation remains the main obstacle to cure. On-target, off-tumor effect of CD19-CAR T leads to side effects such as prolonged B-cell aplasia, limiting the application of therapy in indolent diseases such as chronic lymphocytic leukemia (CLL). Alternative CAR targets and multi-specific CAR are potential solutions to improving cellular therapy outcomes in B-NHL. For Hodgkin lymphoma and T-cell lymphoma, several cell surface antigens have been studied as CAR targets, some of which already showed promising results in clinical trials. Some antigens are expressed by different lymphomas and could be used for designing tumor-agnostic CAR. Here, we reviewed the antigens that have been studied for novel CAR-based therapies, as well as CARs designed to target two or more antigens in the treatment of lymphoma.
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