Language
English
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
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.
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
Published Open-Access
yes
Recommended Citation
Zhu, Fei; Lu, Zheng; Tang, Wenjing; et al., "Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity in Solid Tumors" (2024). Faculty and Staff Publications. 1292.
https://digitalcommons.library.tmc.edu/baylor_docs/1292
Included in
Diseases Commons, Epidemiology Commons, Influenza Humans Commons, Medical Sciences Commons, Oncology Commons