A RECOMBINANT VACCINIA VIRUS EXPRESSING HUMAN PROSTATE-SPECIFIC ANTIGEN (PSA) - SAFETY AND IMMUNOGENICITY IN A NONHUMAN PRIMATE

Prostate-specific antigen (PSA) is a serine protease secreted by prost atic epithelial cells acid is widely used as a marker for prostate can cer. The tissue specificity of PSA makes it a potential target for act ive specific immunotherapy, especially in prostate cancer patients who have undergone prostatectomy and in whom the only PSA-expressing tiss ue in the body resides in metastatic deposits. We report here the clon ing, construction and immunological consequences of immunization of rh esus monkeys with a recombinant vaccinia virus expressing human BSA (d esignated rV-PSA). The prostate gland of the rhesus is structurally an d functionally similar to the human prostate. While rodent and other m ammalian species do not share homology with human PSA, there is 94% ho mology between the amino acid sequences of rhesus and human PSA. Immun ization of rhesus monkeys with wild-type vaccinia virus or rV-PSA elic ited the usual low-grade constitutional symptoms of vaccinia virus inf ection. 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 re ceiving the 10(8)pfu dose of rV-PSA demonstrated PSA-specific T-cell r esponses that were maintained up to 270 days. No differences in anti-P SA 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 i mplications for potential specific immunotherapy protocols using PSA a s a target. (C) 1995 Wiley-Liss, Inc.