Induction of Th1-type immunity and tumor protection with a prostate-specific antigen DNA vaccine.
Prostate specific antigen (PSA) is a serum marker that is widely used in the detection and monitoring of prostate cancer. Though PSA is a self-antigen, T cell responses to PSA epitopes have been detected in healthy men and prostate cancer patients, suggesting it may be used as a target for active immunotherapy of prostate cancer. A PSA DNA vaccine (pPSA) was evaluated in mice and monkeys for its ability to induce antigen-specific immune responses. Mice immunized intradermally with pPSA demonstrated strong PSA-specific humoral and cellular immunity. The anti-PSA immune responses were skewed toward Th1, as shown by high IFNgamma and IL-2 production. The immune response was sufficient to protect mice from challenge with PSA-expressing tumor cells. Tumor protection was durable in the absence of additional vaccination, as demonstrated by protection of vaccinated mice from tumor rechallenge. Furthermore, pPSA vaccination induced PSA-specific antibody titers in male cynomolgus monkeys, which express a closely related PSA gene. These results demonstrate that vaccination with pPSA may be able to break tolerance and can induce an immune response that mediates tumor protection.
Marshall
Deborah J
DJ
Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. dmarsha1@cntus.jnj.com
San Mateo
Lani R
LR
Rudnick
Kelly A
KA
McCarthy
Stephen G
SG
Harris
Michael C
MC
McCauley
Christine
C
Schantz
Allen
A
Geng
Dong
D
Cawood
Pam
P
Snyder
Linda A
LA
D000818:Animals; D000906:Antibodies / Q000097:blood; D005260:Female; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D000906:Antibodies; D019444:Vaccines, DNA; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen