Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses
| Autor: | Niranjan Y. Sardesai, Colleen E. Lucke, Neil J. Cisper, Amir S. Khan, Lindsey Philipson-Weiner, Kendra T. Talbott, Bernadette Ferraro, David B. Weiner |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Enzyme-Linked Immunospot Assay medicine.medical_treatment Immunology Immunization Secondary CD8-Positive T-Lymphocytes Biology urologic and male genital diseases Epitope DNA vaccination Rodent Diseases Interferon-gamma Mice Immune system Antigen Vaccines DNA medicine Animals General Pharmacology Toxicology and Pharmaceutics Mice Inbred BALB C Tumor Necrosis Factor-alpha ELISPOT Immunogenicity Vaccination Prostatic Neoplasms Immunotherapy Prostate-Specific Antigen Disease Models Animal Electroporation Immunization Interleukin-2 Female |
| Zdroj: | Human Vaccines. 7:120-127 |
| ISSN: | 1554-8619 1554-8600 |
| DOI: | 10.4161/hv.7.0.14574 |
| Popis: | Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa. |
| Databáze: | OpenAIRE |
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