肿瘤细胞治疗研究
英文原题：Allogeneic CD20-targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models.
这些临床前数据支持 ADI-001（一种同种异体 CD20 CAR⁺ Vδ1 T 细胞）的临床评价，一项 1 期研究已在 B 细胞恶性肿瘤患者中启动（NCT04735471）。
目的：自体嵌合抗原受体（CAR）T细胞疗法在血液系统恶性肿瘤患者中显示出显著抗肿瘤效力，但并非所有符合条件的患者都能获益。提高患者治疗可及性和临床应答的策略包括使用健康供者预先制备的产品，以及利用具有内在肿瘤杀伤能力的替代效应细胞作为CAR细胞疗法来源。兼具先天性和适应性识别及杀伤恶性细胞机制的T细胞，是异基因CAR T细胞疗法有吸引力的平台。本研究评估异基因外周血来源、表达第二代靶向B细胞特异性抗原CD20 CAR的Vδ1 T细胞（CAR阳性Vδ1 T细胞）的制备可行性和功能。 方法：从供者外周血获取Vδ1 T细胞，在体外活化、扩增并工程化表达新型抗CD20 CAR。采用体外和体内实验评估CD20 CAR阳性Vδ1 T细胞对B细胞肿瘤的CAR依赖性和非依赖性抗肿瘤作用。 结果：抗CD20 CAR阳性Vδ1 T细胞表现出先天性和适应性抗肿瘤活性，包括体外肿瘤细胞杀伤和促炎细胞因子生成，并可在免疫缺陷小鼠中抑制B细胞淋巴瘤异种移植瘤生长。此外，这类细胞未在免疫缺陷小鼠中诱发异种移植物抗宿主病。 结论：这些临床前数据支持对异基因CD20 CAR阳性Vδ1 T细胞产品ADI-001开展临床评估；一项针对B细胞恶性肿瘤患者的Ⅰ期研究已启动（NCT04735471）。
OBJECTIVES: Autologous chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable antitumor efficacy in patients with haematological malignancies; however, not all eligible cancer patients receive clinical benefit. Emerging strategies to improve patient access and clinical responses include using premanufactured products from healthy donors and alternative cytotoxic effectors possessing intrinsic tumoricidal activity as sources of CAR cell therapies. T cells, which combine innate and adaptive mechanisms to recognise and kill malignant cells, are an attractive candidate platform for allogeneic CAR T-cell therapy. Here, we evaluated the manufacturability and functionality of allogeneic peripheral blood-derived CAR + V 1 T cells expressing a second-generation CAR targeting the B-cell-restricted CD20 antigen. METHODS: Donor-derived V 1 T cells from peripheral blood were ex vivo -activated, expanded and engineered to express a novel anti-CD20 CAR. In vitro and in vivo assays were used to evaluate CAR-dependent and CAR-independent antitumor activities of CD20 CAR + V 1 T cells against B-cell tumors. RESULTS: Anti-CD20 CAR + V 1 T cells exhibited innate and adaptive antitumor activities, such as in vitro tumor cell killing and proinflammatory cytokine production, in addition to in vivo tumor growth inhibition of B-cell lymphoma xenografts in immunodeficient mice. Furthermore, CD20 CAR + V 1 T cells did not induce xenogeneic graft-versus-host disease in immunodeficient mice. CONCLUSION: These preclinical data support the clinical evaluation of ADI-001, an allogeneic CD20 CAR + V 1 T cell, and a phase 1 study has been initiated in patients with B-cell malignancies (NCT04735471).
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