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.
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Authors | Munjal Pandya, Kellee Britt, Brad Hoffman, Chen Ling, George V Aslanidi |
Journal | Journal of immunotherapy (Hagerstown, Md. : 1997)
(J Immunother)
Vol. 38
Issue 7
Pg. 292-8
(Sep 2015)
ISSN: 1537-4513 [Electronic] United States |
PMID | 26261893
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Capsid Proteins
- Ovalbumin
|
Topics |
- Animals
- Capsid
(immunology)
- Capsid Proteins
(immunology)
- Cell Line, Tumor
- Dependovirus
(immunology)
- Genetic Therapy
(methods)
- Genetic Vectors
(immunology)
- Immunotherapy
(methods)
- Male
- Mice
- Mice, Inbred C57BL
- Neoplasms
(immunology)
- Ovalbumin
(immunology)
- Prostatic Neoplasms
(immunology)
- T-Lymphocytes
(immunology)
- Transduction, Genetic
(methods)
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