Immunization with PSA/anti-PSA Complexes Induces T and B Cell Responses to PSA in PSA-transgenic Mice (48.19)

Abstract The murine MAb-AR47.47 (IgG1κ) recognizes all circulating forms of PSA and targets the epitope EPEEFLT. In vitro studies showed that human and murine dendritic cells process PSA more efficiently in immune complexes (IC) with MAb-AR47.47. IC induced CD4+ and CD8+ IFN-γ producing T cells, whereas PSA alone or PSA combined with a non-specific antibody mainly stimulated CD4+ T cells. We have further investigated the activation of PSA-specific immune responses with IC in male PSA-transgenic mice, which express human PSA in the prostate. Mice were immunized with PSA and MAb-AR47.47 alone or IC consisting of MAb-AR47.47 and PSA at various concentrations. To investigate the need for foreign antibody in inducing immune responses, rabbit and goat polyclonal anti-PSA antibodies or MAb-AR47.47-ovalbumin were tested in parallel. The mice only generated a weak T helper 2 response to immunization with PSA alone. Robust T helper 1 and 2, CTL and antibody responses were induced in mice immunized with AR47.47-PSA IC. Interestingly, IC with PSA and the polyclonal goat or rabbit antibodies or MAb-AR47.47-ovalbumin induced stronger T helper cell responses to PSA, but resulted in weaker CTL induction relative to IC with MAb-AR47.47. This data indicates that AR47.47-PSA IC can prime B cells, T helper cells and CTL against the tumor antigen PSA in vivo in a setting where PSA is a self antigen.