Tumor antigen-loaded AAV vaccine drives protective immunity in a melanoma animal model

Karina Y Krotova, Hisae Kuoch (Yoshitomi), Colin Caine, George Aslanidi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

We previously described therapeutic opportunities provided by capsid- and expression cassette-optimized adeno-associated virus serotype 6 (AAV6) vectors to suppress tumor growth in both solid and metastatic mouse models by using artificial ovalbumin (OVA) immunogen. In the current study, we further elucidated the mechanism of function of a novel AAV-based vaccine loaded with the melanoma tumor-associated antigens premelanosome protein gp100, tyrosinase (Tyr), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (TRP2). We showed that the AAV6-based vaccine creates cellular and humoral antigen-specific responses, while antigen expression at the site of vaccine injection was temporal, and the clearance of antigen coincided with T cell infiltration. Our data revealed the superior protective immune response of optimized AAV6-TRP1 compared with other self-antigens in a disease-free mouse model. We further assessed the ability of AAV6-TRP1 to protect animals from metastatic spread in the lungs and to extend animal survival by inhibiting solid tumor growth. Flow cytometry-based analysis indicated significant infiltration of CD8+ T cells and natural killer (NK) cells in the tumor site, as well as changes in the polarization of intratumoral macrophages. Altogether, our data strongly support the use of optimized AAV vectors for cancer vaccine development.

Original languageEnglish (US)
Pages (from-to)301-311
Number of pages11
JournalMolecular Therapy Methods and Clinical Development
Volume28
DOIs
StatePublished - Mar 9 2023

Bibliographical note

Funding Information:
This project was supported by Paint the Town Pink (PTTP) pilot grant ( GA ), Fifth District Eagles Cancer Telethon Postdoctoral Fellowship Award (HK), and startup funds from the Hormel Institute (G.A.).

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • adeno-associated virus
  • antigen-specific T cell
  • cancer vaccine
  • protective immune response
  • self-antigen
  • syngeneic animal model

PubMed: MeSH publication types

  • Journal Article

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