Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years, but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone. In this study, an oncolytic virus (rVSV-LCMVG) that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells. By transforming the immunosuppressive tumor microenvironment into an immunosensitive one, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy. This occurred whether the OV was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8⁺ T cells to the TME to trigger antitumor immune responses. Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD-1, and restoring effector T-cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells. The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival. This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

基于过继转移T细胞或溶瘤病毒的抗肿瘤疗法近年来取得了显着进展，但其浸润实体瘤的效率有限，导致单独使用时难以达到预期的抗肿瘤效果。在这项研究中，设计了一种不易诱导病毒中和抗体的溶瘤病毒（rVSV-LCMVG），并将其与过继转移的T细胞结合。通过将免疫抑制的肿瘤微环境转变为免疫敏感的环境，在 B16 荷瘤小鼠中，联合治疗显示出比单一治疗更优异的抗肿瘤效果。无论 OV 是瘤内注射还是静脉注射，都会发生这种情况。联合疗法显着增加了肿瘤内细胞因子和趋化因子的水平，并将 CD8 ⁺ T 细胞募集到 TME 以触发抗肿瘤免疫反应。使用过继转移的 T 细胞进行预处理，然后进行溶瘤病毒疗法，通过促进 T 细胞募集、下调 PD-1 的表达和恢复效应 T 细胞功能，使难治性肿瘤变得敏感。为了提供具有更大转化价值的联合疗法，引入了 mRNA 疫苗来诱导肿瘤特异性 T 细胞，而不是过继转移的 T 细胞。 OV 和 mRNA 疫苗的组合还显示出肿瘤负荷的显着降低和生存期的延长。本研究从协同功效和机制方面提出了OV与过继性T细胞转移或编码肿瘤相关抗原的mRNA疫苗的合理联合治疗。