PDF(Pubmed)
Abstract：
Recent studies have indicated that combining oncolytic viruses with CAR-T cells in therapy has shown superior anti-tumor effects, representing a promising approach. Nonetheless, the localized delivery method of intratumoral injection poses challenges for treating metastatic tumors or distal tumors that are difficult to reach. To address this obstacle, we employed HSV-1-infected CAR-T cells, which systemically delivery HSV into solid tumors. The biological function of CAR-T cells remained intact after loading them with HSV for a period of three days. In both immunocompromised and immunocompetent GBM orthotopic mouse models, B7-H3 CAR-T cells effectively delivered HSV to tumor lesions, resulting in enhanced T-cell infiltration and significantly prolonged survival in mice. We also employed a bilateral subcutaneous tumor model and observed that the group receiving intratumoral virus injection exhibited a significant reduction in tumor volume on the injected side, while the group receiving intravenous infusion of CAR-T cells carrying HSV displayed suppressed tumor growth on both sides. Hence, CAR-THSV cells offer notable advantages in the systemic delivery of HSV to distant tumors. In conclusion, our findings emphasize the potential of CAR-T cells as carriers for HSV, presenting significant advantages for oncolytic virotherapy targeting distant tumors.
摘要：
最近的研究表明，溶瘤病毒与CAR-T细胞联合治疗已显示出优异的抗肿瘤效果，代表一种有希望的方法。尽管如此，肿瘤内注射的局部给药方法对治疗难以触及的转移性肿瘤或远端肿瘤提出了挑战.为了解决这个障碍，我们使用HSV-1感染的CAR-T细胞，将HSV全身递送到实体瘤中。在用HSV加载CAR-T细胞三天后,其生物学功能保持完整。在免疫受损和免疫活性GBM原位小鼠模型中，B7-H3CAR-T细胞有效地将HSV递送至肿瘤病变，导致T细胞浸润增强，并显着延长小鼠的生存期。我们还采用了双侧皮下肿瘤模型，观察到接受肿瘤内病毒注射的组在注射侧肿瘤体积显着减少，而接受静脉输注携带HSV的CAR-T细胞的组显示两侧肿瘤生长受到抑制。因此，CAR-THSV细胞在HSV向远处肿瘤的全身递送中提供显著优势。总之,我们的发现强调了CAR-T细胞作为HSV携带者的潜力，针对远处肿瘤的溶瘤病毒疗法具有显著优势。
