Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity in Solid Tumors

Authors

Fei Zhu
Zheng Lu
Wenjing Tang
Guangya Zhao
Yingxiang Shao
Bowen Lu
Jiage Ding
Yanyan Zheng
Lin Fang
Huizhong Li
Gang Wang
Renjin Chen
Junnian Zheng
Dafei Chai

Publication Date

8-28-2024

Journal

The Journal for ImmunoTherapy of Cancer

DOI

10.1136/jitc-2024-009869

PMID

39209449

PMCID

PMC11367354

PubMedCentral® Posted Date

8-28-2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Animals, Mice, Humans, Cancer Vaccines, Aurora Kinase A, Adenoviridae, Cell Line, Tumor, Cyclin-Dependent Kinase-Activating Kinase, Female, Neoplasms, Adenovirus Vaccines, CD8-Positive T-Lymphocytes

Abstract

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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