A recombinant vaccinia virus expressing human prostate-specific antigen (PSA): safety and immunogenicity in a non-human primate.
Prostate-specific antigen (PSA) is a serine protease secreted by prostatic epithelial cells and is widely used as a marker for prostate cancer. The tissue specificity of PSA makes it a potential target for active specific immunotherapy, especially in prostate cancer patients who have undergone prostatectomy and in whom the only PSA-expressing tissue in the body resides in metastatic deposits. We report here the cloning, construction and immunological consequences of immunization of rhesus monkeys with a recombinant vaccinia virus expressing human PSA (designated rV-PSA). The prostate gland of the rhesus is structurally and functionally similar to the human prostate. While rodent and other mammalian species do not share homology with human PSA, there is 94% homology between the amino acid sequences of rhesus and human PSA. Immunization of rhesus monkeys with wild-type vaccinia virus or rV-PSA elicited the usual low-grade constitutional symptoms of vaccinia virus infection. There was no evidence of any adverse effects in any immunized monkeys. A short-lived PSA-specific IgM antibody response was noted in all rV-PSA immunized monkeys regardless of dose level. All monkeys receiving the 10(8)pfu dose of rV-PSA demonstrated PSA-specific T-cell responses that were maintained up to 270 days. No differences in anti-PSA immune responses or toxicity were observed in animals that received prostatectomy prior to immunization. Our results thus demonstrate the safety and immunogenicity of rV-PSA in a non-human primate and have implications for potential specific immunotherapy protocols using PSA as a target.
Hodge
J W
JW
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA.
Schlom
J
J
Donohue
S J
SJ
Tomaszewski
J E
JE
Wheeler
C W
CW
Levine
B S
BS
Gritz
L
L
Panicali
D
D
Kantor
J A
JA
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus
D000912:Antibodies, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D017430:Prostate-Specific Antigen