Inhibition of prostate cancer growth by immunization with a GM-CSF-modified mouse prostate cancer RM-1 cell vaccine in a novel murine model.

Abstract

Advanced prostate cancer is difficult to treat owing to a lack of effective approaches for disrupting immune tolerance. C57BL/6 male and female mice implanted with viable RM-1 cells represent a novel murine model of advanced prostate cancer for studying antitumor effects following immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-modified RM-1 cell vaccine, which has been described previously. In vitro cytotoxic activity and cytokine secretion experiments were conducted to investigate the antitumor response. The cytotoxicity profile of splenocytes from female mice immunized against RM-1 cells primarily involved cytotoxic T lymphocyte (CTL) lysis and, to a lesser extent, natural killer (NK) cell lysis. NK cell lysis was also observed in males, which exhibited no evidence of CTL lysis. The secretion of interferon-γ in the GM-CSF-modified cell vaccine group was significantly increased compared with the other groups. The level of interleukin-4 was low. To investigate the antitumor immune response further, cluster of differentiation 4 (CD4) T cells and CD8 T cells were analyzed in the spleens and tumors of female mice receiving the GM-CSF-modified RM-1 cell vaccine. Unlike female mice, males exhibited the highest proportion of NK cells in the spleen. NK cells were not detected in the tumor tissue in any of the groups. The difference between the sexes may explain the specificity of the immune response, as females are intolerant to prostate antigens whereas males are. This model is clinically relevant as it translates to human immunology and offers an effective and convenient method for studying immunotherapy for prostate cancer.