肿瘤细胞治疗研究
英文原题：CCR5-targeted allogeneic gamma-delta CD19 chimeric antigen receptor T cells for HIV-associated B cell-malignancy immunotherapy.
基于免疫的细胞疗法为癌症治疗提供了一种有前景的方法。
基于免疫的细胞疗法为肿瘤治疗提供了有前景的方法。自体嵌合抗原受体（CAR）T 细胞虽已取得成功，但生产耗时、成本高且需为患者单独制备。γδ T 细胞有望用于现货型 CAR-T 细胞治疗，但其临床转化受细胞频率低、难以进行基因操作及扩增后分化程度较高等因素阻碍，限制了治疗可行性。本研究展示了一种体外活化和扩增外周血 T 细胞的方法，可实现较高基因编辑率及高效 CAR 整合。通过人工抗原呈递细胞，我们制备出分化程度较低、功能较强的 CAR-T 细胞。将 FDA 批准的 CD19 CAR 靶向整合至 CCR5 位点后，我们获得 CCR5 缺失的 CD19 CAR-T 细胞（CCR5KI-CAR19）；该细胞可抵抗 HIV 介导的清除，并对 B 细胞淋巴瘤和白血病产生强效抗肿瘤应答。CCR5KI-CAR19 T 细胞可用于 HIV 相关 B 细胞恶性肿瘤的免疫治疗。这些研究提供了临床前证据，支持大规模开发具有强效的异基因 CAR-T 细胞，以用于多种免疫治疗。
Immune-based cell therapy offers a promising approach to cancer treatment. While autologous chimeric antigen receptor (CAR) T cells have shown success, production is time-consuming, costly and patient specific. Gamma-delta ( ) T cells are promising for 'off-the-shelf' CAR T cell therapy. However, clinical translation of CAR T cells is hampered by low frequency, resistance to genetic manipulation and advanced differentiation after expansion, limiting therapeutic feasibility. Here we demonstrate a method for in vitro activation and expansion of peripheral blood T cells, facilitating high rates of gene editing and efficient CAR integration. Using artificial antigen-presenting cells, we produce minimally differentiated, highly functional CAR T cells. By targeting a US Food and Drug Administration-approved CD19 CAR to the CCR5 locus, we generate CCR5-deficient CD19 CAR T cells ( CCR5KI-CAR19), which demonstrated resistance to HIV-mediated depletion and robust antitumour responses against B cell lymphoma and leukaemia. CCR5KI-CAR19 T cells enable the immunotherapy of HIV-associated B cell malignancies. These studies provide preclinical evidence supporting large-scale development of potent allogeneic CAR T cells for diverse immunotherapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
