肿瘤细胞治疗研究
英文原题：Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently.
CD19 嵌合抗原受体（CAR）T 细胞在复发和难治性急性淋巴细胞白血病（R/R ALL）中显示出强大疗效，但在慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL）中结果不佳。
CD19 嵌合抗原受体（CAR）T 细胞在复发和难治性急性淋巴细胞白血病（R/R ALL）中显示出强大疗效，但在慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL）中结果不佳。CD19 复发以及导致治疗失败的 CAR-T 细胞持久性缺乏，是亟待克服的重大障碍。靶向 CD20 的 CAR-T 是挽救 CD19 CAR-T 失败的一种选择。既往研究已建立可避免抗原丢失和免疫逃逸的双特异性 CAR-T 的变异结构。在此，我们构建了同时靶向 CD19 和 CD20 抗原的串联和环状 CAR 结构。双特异性 CAR-T 细胞可清除 CD19 或 CD20 阴性淋巴瘤细胞，表明它们表现出对 CD19 和 CD20 的双抗原靶向。通过比较四种双特异性 CAR 修饰 T 细胞的效率，发现 loop2019 CAR 是其中最佳结构，可在体外以极低剂量根除淋巴瘤细胞系以及患者原代淋巴瘤或 CLL 细胞，并在淋巴瘤异种移植小鼠模型中显著延长生存时间。这些数据凸显了 loop2019 CAR-T 在临床治疗中的潜力。
CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome. CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients' primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.
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