针对免疫检查点的疫苗代表了一种有前途的实体瘤免疫治疗方法。然而，双靶向免疫检查点在肾癌中的治疗效果仍不清楚。开发了针对B7H1和B7H3的腺病毒（Ad）疫苗，并利用流式细胞术评估了其在皮下、肺转移或原位肾癌小鼠和人源化模型中的治疗效果细胞计数、酶联免疫吸附点 (ELISPOT)、细胞毒性 T 淋巴细胞 (CTL) 杀伤、细胞缺失、苏木精和伊红 (HE) 染色以及免疫组织化学 (IHC) 检测。Ad-B7H1/B7H3 免疫有效抑制肿瘤生长并增加皮下肿瘤模型中 CD8 T 细胞的诱导和百分比。该疫苗增强了CD11c或CD8 CD11c细胞的诱导和成熟，促进肿瘤特异性CD8 T细胞免疫反应。 CD8 T 细胞增殖增加和 CTL 杀伤活性增强证明了这一点。体内 CD8 T 细胞的缺失消除了 Ad-B7H1/B7H3 疫苗的抗肿瘤作用，凸显了功能性 CD8 T 细胞免疫反应的关键作用。此外，通过多功能CD8 T细胞免疫应答，Ad-B7H1/B7H3疫苗在肺转移、原位和人源化肿瘤模型中观察到显着的治疗效果。针对双重免疫检查点B7H1和B7H3的Ad疫苗对肾病发挥了有效的治疗作用。癌症并有望用于实体瘤治疗。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Vaccines targeting immune checkpoints represent a promising immunotherapeutic approach for solid tumors. However, the therapeutic efficacy of dual targeting immune checkpoints is still unclear in renal carcinoma.An adenovirus (Ad) vaccine targeting B7H1 and B7H3 was developed and evaluated for its therapeutic efficacy in subcutaneous, lung metastasis or orthotopic renal carcinoma mouse and humanized models using flow cytometry, Enzyme-linked immunosorbent spot (ELISPOT), cytotoxic T lymphocyte (CTL) killing, cell deletion, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) assays.The Ad-B7H1/B7H3 immunization effectively inhibited tumor growth and increased the induction and percentages of CD8+ T cells in subcutaneous tumor models. The vaccine enhanced the induction and maturation of CD11c+ or CD8+CD11c+ cells, promoting tumor-specific CD8+ T cell immune responses. This was evidenced by increased proliferation of CD8+ T cells and enhanced CTL killing activity. Deletion of CD8+ T cells in vivo abolished the anti-tumor effect of the Ad-B7H1/B7H3 vaccine, highlighting the pivotal role of functional CD8+ T cell immune responses. Moreover, significant therapeutic efficacy of the Ad-B7H1/B7H3 vaccine was observed in lung metastasis, orthotopic, and humanized tumor models through multifunctional CD8+ T cell immune responses.The Ad vaccine targeting dual immune checkpoints B7H1 and B7H3 exerts a potent therapeutic effect for renal carcinoma and holds promise for solid tumor treatment.Copyright © 2024 Elsevier B.V. All rights reserved.