以免疫检查点疗法为基础的免疫治疗在癌症治疗领域取得了重要进展，但其治疗效果仍存在一定的局限性。为了治疗肾癌，我们开发了一种编码肿瘤抗原碳酸酐酶IX（CAIX）的复制缺陷腺病毒(Ad)疫苗，结合编码免疫检查点PD-L1的Ad疫苗。建立了三个肿瘤模型：皮下肿瘤、肺转移和原位肿瘤，并使用Ad疫苗注射治疗，评估了疫苗的治疗效果。与单独使用Ad疫苗组相比，Ad-CAIX/Ad-PD-L1的组合疫苗显著减少了皮下肿瘤的生长。Ad-CAIX/Ad-PD-L1的联合免疫注射增强了脾脏和肿瘤中CD11c+或CD8+CD11c+树突状细胞的诱导和成熟，并促进了强烈的肿瘤特异性CD8+ T细胞免疫反应。体内CD8 T细胞删除实验显示，Ad-CAIX/Ad-PD-L1疫苗的抗肿瘤效应主要依赖功能性CD8+ T细胞免疫反应。此外，Ad-CAIX/Ad-PD-L1疫苗在转移性或原位模型中有效抑制了肿瘤生长和肺转移。这些结果表明，免疫检查点疫苗的组合策略作为恶性肿瘤治疗方法具有很大的应用潜力。© 2023. Springer Nature Limited。

Immune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine's therapeutic effect. Compared to the single Ad vaccine group, the subcutaneous tumor growth was significantly reduced in Ad-CAIX/Ad-PD-L1 combination group. Co-immunization of Ad-CAIX/Ad-PD-L1 enhanced the induction and maturation of CD11c+ or CD8+CD11c+ DCs in the spleen and tumor and promoted the strong tumor-specific CD8+ T cell immune responses. In vivo CD8 T cell deletion assay showed that the anti-tumor effect of the Ad-CAIX/Ad-PD-L1 vaccine was mainly dependent on functional CD8+ T cell immune responses. Furthermore, the Ad-CAIX/Ad-PD-L1 vaccine effectively inhibited tumor growth and lung metastasis in metastatic or orthotopic models. These results indicate that the combination strategy of the immune checkpoint vaccine shows promising potential as an approach for malignant tumor therapy.© 2023. Springer Nature Limited.