Novel therapeutic strategies for advanced ovarian cancer by using induced pluripotent stem cell-derived myelomonocytic cells producing interferon beta

Abstract

Although first-line chemotherapy has a high rate of complete responses in ovarian cancer patients, the vast majority of patients present with recurrent disease that has become refractory to conventional chemotherapy. Peritoneal dissemination and malignant ascites are the hallmarks of recurrent or advanced ovarian cancer and severely reduce quality of life. Development of therapeutic measures to treat such patients is eagerly anticipated. Macrophage infiltration is observed in various types of cancer including epithelial ovarian cancer. In addition, macrophages are involved in the formation of spheroids in the malignant ascites of ovarian cancer and promote cancer growth. iPS-ML, macrophage-like myelomonocytic cells generated from human induced pluripotent stem (iPS) cells, made close contacts with ovarian cancer cells in vitro. We hypothesized that, if we inoculate iPS-ML-producing IFN-β (iPS-ML/IFN-β) into the peritoneal cavity of patients with ovarian cancer, IFN-β produced by the iPS-ML/IFN-β would efficiently act on the cancer cells to suppress cancer growth. To evaluate this hypothesis, we injected iPS-ML/IFN-β into SCID mice bearing peritoneally disseminated human ovarian cancer cells, SKOV3. Immunohistochemical analysis of the intraperitoneal tumors detected iPS-ML/IFN-β infiltrating into the cancer tissues. Therapy with iPS-ML/IFN-β significantly suppressed tumor progression. In addition, dramatic reduction of cancer-related ascites was observed. Collectively, it is suggested that iPS-ML/IFN-β therapy offers a new approach for the treatment of patients with advanced ovarian cancer.