Reprogramming immune response with capsid-optimized AAV6 vectors for immunotherapy of cancer

Munjal Pandya, Kellee Britt, Brad Hoffman, Chen Ling, George V. Aslanidiwz

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In the current studies we generated novel capsid-optimized adeno-associated virus (AAV) serotype 6 (AAV6) vectors expressing a tumor-associated antigen, and assessed their ability to activate a protective T-cell response in an animal model. First, we showed that specific mutations in the AAV6 capsid increase the transduction efficiency of these vectors in mouse bone marrow-derived dendritic cells in vitro for approximately 5-fold compared with the wild-type (WT) AAV6 vectors. Next, we evaluated the ability of the mutant AAV6 vectors to initiate specific T-cell clone proliferation in vivo. Our data indicate that the intramuscular administration of AAV6-S663V+T492V vectors expressing ovalbumin (OVA) led to a strong activation (approximately 9%) of specific T cells in peripheral blood compared with AAV6-WT treated animals (<1%). These OVA-specific T cells have a superior killing ability against mouse prostate cancer cell line RM1 stably expressing the OVA antigen when propagated in vitro. Finally, we evaluated the ability of capsid-optimized AAV6-S663V+ T492V vectors to initiate a protective anticancer immune response in vivo. Our results document the suppression of subcutaneous tumor growth in animals immunized with AAV6-S663V+ T492V vectors expressing prostatic acid phosphatase (PAP) for approximately 4 weeks in comparison with 1 week and 2 weeks for the negative controls, AAV6-EGFP, and AAV6-WT-PAP treated mice, respectively. These studies suggest that successful inhibition of tumor growth in an animal model would set the stage for potential clinical application of the capsid-optimized AAV6-S663V+T492V vectors.

Original languageEnglish (US)
Pages (from-to)292-298
Number of pages7
JournalJournal of Immunotherapy
Volume38
Issue number7
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

  • Adeno-associated virus vectors
  • Dendritic cells
  • Gene expression
  • Prostate cancer
  • Prostatic acid phosphatase
  • Vaccine

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