Anti-MUC1 antibody responses in endometriosis and ovarian cancer in humans and preclinical MUC1 transgenic models (88.29)

Abstract Ovarian cancer is the deadliest gynecologic malignancy and endometriosis is the only currently described precursor lesion. MUC1 mucin is an ovarian epithelial tumor-associated antigen and a vaccine candidate for ovarian cancer immunotherapy. Natural and vaccine-induced MUC1 immunity, often studied in ovarian cancer is much less understood in endometriosis. Human and murine mucin 1 share little homology in the extracellular region and transgenic mouse models expressing the human antigen are needed. We generated two novel preclinical models for MUC1 positive endometriosis and MUC1-expressing ovarian tumors, respectively. The MUC1KrasG12D mice develop MUC1-positive ovarian endometriosis after AdCre injection under the ovarian bursa. MUC1KrasG12D transgenic mice injected with MUC1-expressing immortalized ovarian surface epithelial cells (OSE) develop tumors throughout the peritoneal cavity and serve as a transplantable in vivo tumor model. Our results show that MUC1 is immunogenic in humans and mice with either malignant or premalignant lesions and triggers MUC1-specific IgM and Th2-driven IgG antibodies. Furthermore, the presence of IgG in cancer patients correlates inversely with survival. In additions, mice and humans show several differences in immune regulation by other CD4 T cell subsets (Th17, Treg) with consequences for MUC1 vaccination in preclinical models. PA Dept of Health, CMRF.