One potential use for
prostate-cancer-associated genes discovered through ongoing genetics studies entails the construction of virus- or plasmid-based recombinant vector
vaccines encoding these new
tumor-associated
antigens (TAA) to induce TAA-specific immune responses for the prevention or
therapy of
prostate cancer. Clinical trials evaluating prototypes of such
recombinant vaccines are under way. TAA-encoding recombinant vector
vaccines, however, have not previously been evaluated in a
prostate-cancer animal model. For assessment of the potential susceptibility of
prostate cancer to genetic immunization strategies using TAA-encoding recombinant vectors, the antitumor efficacy of a model recombinant viral vector encoding a TAA was evaluated in rat Dunning
prostate cancer. Recombinant
vaccinia was chosen as a prototype virus vector encoding a TAA for these studies, and
beta-galactosidase was chosen as a model target TAA. Dunning AT-2 cells were transduced with a retroviral vector to express
beta-galactosidase, and the susceptibility of tumorigenic AT-2-lacZ cells to immunization with
vaccinia-lacZ was measured using protection studies in Copenhagen and nu/nu rats. Stably transduced AT-2-lacZ cells expressing
beta-galactosidase as measured by enzymatic substrate-based assays were found to retain their tumorigenicity in vivo despite abundant expression of rat major histocompatibility complex (MHC) class I. Immunization with model TAA-encoding recombinant
vaccinia-lacZ conferred significant protection against subsequent growth of AT-2-lacZ cells in vivo (P = 0.01); however, the efficacy of such immunization was markedly dependent on the volume of
tumor challenge. The antitumor efficacy of TAA-encoding recombinant
vaccinia immunization was abrogated in nu/nu rats, suggesting a T-cell-dependent mechanism of activity. These studies suggest that
prostate cancer may be a suitable target for immunization strategies using TAA-encoding recombinant vectors. Such immunization strategies may be more effective in settings of minimal
cancer burden.