肿瘤细胞治疗研究
英文原题：An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ.
An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ.
TIL（肿瘤浸润淋巴细胞）疗法的全部潜力一直受制于 TIL 活化不足、持久性低以及肿瘤新抗原呈递效率低下。
TIL（肿瘤浸润淋巴细胞）疗法的全部潜力受到多方面限制，包括 TIL 活化不足、持续存在能力较低以及肿瘤新抗原呈递效率低。本研究使用编码 OX40L 和 IL12 的单纯疱疹病毒 1 型（HSV-1）溶瘤病毒（OV-OX40L/IL12）感染肿瘤细胞，将其转化为人工抗原呈递细胞（aAPC），为 T 细胞充分活化提供局部信号。感染后的肿瘤细胞抗原呈递细胞相关标志物表达增加，与 TIL 共培养时诱导更强 T 细胞活化和杀伤。OV-OX40L/IL12 联合 TIL 疗法在患者来源异种移植和同系小鼠肿瘤模型中诱导肿瘤完全消退，并产生抗肿瘤免疫记忆。此外，联合治疗使肿瘤细胞具备 aAPC 特性、活化 T 细胞，并将肿瘤微环境中的巨噬细胞重编程为更偏 M1 样表型。这一联合策略释放了 TIL 疗法的全部潜力，值得进一步开展临床研究。
The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.
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