Department of Hematology and Oncology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
ProCure Program, IDIBELL-Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Spain.
Front Immunol. 2018 Oct 23;9:2460. doi: 10.3389/fimmu.2018.02460. eCollection 2018.
Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has resulted in unprecedented rates of long-lasting complete responses in patients with leukemia and lymphoma. However, despite the impressive results in patients with hematologic malignancies, CAR-T cells have showed limited effect against solid cancers. New approaches will need to simultaneously overcome the multiple challenges that CAR-T cells encounter in solid tumors, including the immunosuppressive tumor microenvironment and heterogeneity of antigen expression. Oncolytic viruses are lytic and immunogenic anti-cancer agents with the potential to synergize with CAR-T cells for the treatment of solid tumors. In addition, viruses can be further modified to deliver therapeutic transgenes selectively to the tumor microenvironment, which could enhance the effector functions of tumor-specific T cells. This review summarizes the major limitations of CAR-T cells in solid tumors and discusses the potential role for oncolytic viruses as partners for CAR-T cells in the fight against cancer.
嵌合抗原受体 (CAR)-修饰 T 细胞的过继转移已在白血病和淋巴瘤患者中产生了前所未有的持久完全缓解率。然而，尽管在血液恶性肿瘤患者中取得了令人印象深刻的结果，但 CAR-T 细胞对实体瘤的疗效有限。新方法将需要同时克服 CAR-T 细胞在实体肿瘤中遇到的多个挑战，包括免疫抑制性肿瘤微环境和抗原表达的异质性。溶瘤病毒是溶瘤和免疫原性的抗癌药物，有可能与 CAR-T 细胞协同作用，用于治疗实体瘤。此外，病毒可以进一步修饰以选择性地将治疗性转基因递送到肿瘤微环境中，从而增强肿瘤特异性 T 细胞的效应功能。本文综述了 CAR-T 细胞在实体肿瘤中的主要局限性，并讨论了溶瘤病毒作为 CAR-T 细胞在抗癌斗争中的伙伴的潜在作用。
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