Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors.
J Immunother Cancer
; 12(8)2024 Aug 28.
Article
in En
| MEDLINE
| ID: mdl-39209449
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cancer Vaccines
/
Aurora Kinase A
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Immunother Cancer
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom