Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine.
BACKGROUND
Prostate cancer is the most common malignancy in Swedish and American men. Effective curative treatment modalities are debilitating and available only for localized disease. As an immunotherapy approach, DNA encoding prostate-specific antigen (PSA), was used to immunize mice and induce PSA-specific cellular immunity.


METHODS
A plasmid expressing PSA, alone or in combination with plasmids coding for GM-CSF and/or IL-2, was used for DNA immunization. Cr-release, intracellular IFN-gamma cytokine staining, and tumor challenge assays were used to evaluate the immune response.


RESULTS
The DNA vaccine induces PSA-specific cytotoxic T lymphocytes (CTLs) and when co-injected with IL-2 and GM-CSF it protects four of five mice against a PSA-expressing tumor challenge.


CONCLUSIONS
We demonstrate that immunization with a PSA DNA vaccine can evoke PSA-specific cellular immune responses. We also show, for the first time, that a PSA DNA vaccine can induce anti-tumor immunity in vivo.
Roos
Anna-Karin
AK
Department of Oncology and Pathology, Cancer Center Karolinska, Immune and Gene Therapy Laboratory, Karolinska Institute, Stockholm, Sweden.
Pavlenko
Maxim
M
Charo
Jehad
J
Egevad
Lars
L
Pisa
Pavel
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007376:Interleukin-2; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen