An Engineered AAV6-Based Vaccine Induces High Cytolytic Anti-Tumor Activity by Directly Targeting DCs and Improves Ag Presentation

Karina Krotova, Andrew Day, George Aslanidi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

We have previously shown that an AAV6-based vaccine generates high levels of antigen-specific CD8+ T cells. Further modifications described here led to significantly increased levels of antigen-specific CD8+ and CD4+ T cells, enhanced formation of memory cells, and superior antigen-specific killing capacity in a murine model. By tracking reporter-gene-positive dendritic cells, we showed that they were directly targeted with modified AAV6 in vivo. Our vaccine's anti-cancer potential was evaluated with the antigen ovalbumin against a B16F10 melanoma cell line stably expressing ovalbumin. The vaccination showed superior protection in a murine model of metastatic melanoma. The vaccination significantly delayed solid tumor growth but did not completely prevent tumor development. We show that tumors in immunized mice escaped vaccine-induced killing by losing ovalbumin expression. The vaccine induced massive tumor infiltration with NK and CD8+ T cells with upregulated PD-1 expression. Thus, a vaccination of a combination of anti-PD-1 antibodies demonstrated significant improvement in the treatment efficacy. To summarize, we showed that a bioengineered AAV6-based vaccine elicits strong and long-lasting cellular and humoral responses against an encoded antigen. To increase AAV vaccine efficiency and mitigate tumor escape through antigen loss, we intended to target several antigens in combination with treatments targeting the tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)166-177
Number of pages12
JournalMolecular Therapy - Oncolytics
Volume15
DOIs
StatePublished - Dec 20 2019

Bibliographical note

Funding Information:
This project is supported by startup funds from the Hormel Institute . The authors thank Josh Moth for editing the manuscript.

Publisher Copyright:
© 2019 The Author(s)

Keywords

  • Adeno-associated virus
  • anti-cancer vaccine
  • dendritic cells
  • melanoma

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