Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.
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.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Bernadette
B
Ferraro
Neil J
NJ
Cisper
Kendra T
KT
Talbott
Lindsey
L
Philipson-Weiner
Colleen E
CE
Lucke
Amir S
AS
Khan
Niranjan Y
NY
Sardesai
David B
DB
Weiner
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018274:Electroporation / Q000379:methods*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D007117:Immunization, Secondary / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000628:therapy*; D012376:Rodent Diseases / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen