靶向激酶提供了治疗实体瘤的潜在策略；然而，针对激酶的疫苗的治疗潜力仍不确定。开发了编码极光激酶A（AURKA）或细胞周期蛋白依赖性激酶7（CDK7）的腺病毒（Ad）疫苗，并通过蛋白质印迹、流式细胞术等多种方法研究了其治疗潜力在小鼠和人源化实体瘤模型中进行细胞计数、细胞毒性 T 淋巴细胞测定和酶联免疫斑点 (ELISpot)。Ad-AURKA/CDK7 联合免疫可有效阻止 Renca、RM-1、MC38 和 Hepa1 的皮下肿瘤生长-6个肿瘤模型。在治疗性肿瘤模型中，Ad-AURKA/CDK7 治疗可阻止肿瘤生长并增加免疫细胞浸润。 Ad-AURKA/CDK7 的施用促进了树突状细胞亚群的诱导和成熟，并增强了多功能 CD8 T 细胞抗肿瘤免疫。此外，该疫苗通过促进记忆 CD8 T 细胞的生成，诱导持久的抗肿瘤作用。 CD8 T 细胞耗竭后的肿瘤恢复强调了这些细胞在观察到的治疗效果中不可或缺的作用。通过诱导多功能 CD8 T 细胞抗肿瘤免疫反应，Ad-AURKA/CDK7 疫苗的有效功效在肺转移、原位和人源化肿瘤模型中得到了一致证明。我们的研究结果表明，针对双激酶 AURKA 的 Ad-AURKA/CDK7 疫苗CDK7 成为治疗实体瘤的一种有前途且有效的治疗方法。© 作者（或其雇主）2024。根据 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of Ad-AURKA/CDK7 promoted the induction and maturation of dendritic cell subsets and augmented multifunctional CD8+ T-cell antitumor immunity. Furthermore, the vaccine induced a long-lasting antitumor effect by promoting the generation of memory CD8+ T cells. Tumor recovery on CD8+ T-cell depletion underscored the indispensable role of these cells in the observed therapeutic effects. The potent efficacy of the Ad-AURKA/CDK7 vaccine was consistently demonstrated in lung metastasis, orthotopic, and humanized tumor models by inducing multifunctional CD8+ T-cell antitumor immune responses.Our findings illustrate that the Ad-AURKA/CDK7 vaccine targeting dual kinases AURKA and CDK7 emerges as a promising and effective therapeutic approach for the treatment of solid tumors.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.