Abstract
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.
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