Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies, but solid tumors continue to pose significant challenges. Oncolytic viruses (OVs) have generated significant excitement in the field of cancer treatment recently. In particular, OVs can help CAR T cells overcome some of the immunosuppressive mechanisms within the tumor microenvironment through OV intrinsic effects or delivery of immunostimulatory agents. Numerous preclinical studies demonstrate that combining CAR T cells with OVs can increase CAR T cell trafficking, antitumor activity, and elimination of antigen-negative tumor cells. Despite promising preclinical results, only one clinical trial (NCT03740256) investigating CAR T and OV combination therapy is underway, highlighting the challenges of translating this approach to the clinic. Antiviral immunity and the route of OV administration, in addition to concerns about cost and safety, limit the clinical application of this approach. Strategies to reduce the production cost of both CAR T cells and OVs, as well as molecularly modifying OVs to enhance their bioavailability, will likely encourage further exploration of this combination therapy in clinical trials.

中文翻译：

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溶瘤病毒与嵌合抗原受体 T 细胞疗法相结合

嵌合抗原受体 (CAR) T 细胞疗法彻底改变了血液恶性肿瘤的治疗，但实体瘤仍然面临重大挑战。溶瘤病毒（OV）最近在癌症治疗领域引起了极大的关注。特别是，OV可以通过OV的内在作用或免疫刺激剂的递送来帮助CAR T细胞克服肿瘤微环境内的一些免疫抑制机制。大量临床前研究表明，CAR T 细胞与 OV 结合可以增加 CAR T 细胞运输、抗肿瘤活性和消除抗原阴性肿瘤细胞。尽管临床前结果有希望，但只有一项研究 CAR T 和 OV 联合疗法的临床试验 (NCT03740256) 正在进行中，这凸显了将这种方法转化为临床的挑战。除了成本和安全性方面的担忧之外，抗病毒免疫和 OV 给药途径也限制了这种方法的临床应用。降低 CAR T 细胞和 OV 的生产成本以及对 OV 进行分子修饰以提高其生物利用度的策略可能会鼓励在临床试验中进一步探索这种联合疗法。