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

• Published in: Cancer science Vol. 109; no. 11; pp. 3403 - 3410
• Main Authors: Imamura, Yuko, Tashiro, Hironori, Tsend‐Ayush, Gandolgor, Haruta, Miwa, Dashdemberel, Narantuya, Komohara, Yoshihiro, Tsuboki, Junko, Takaishi, Kiyomi, Ohba, Takashi, Nishimura, Yasuharu, Katabuchi, Hidetaka, Senju, Satoru
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-11-2018; John Wiley and Sons Inc
• Subjects: Angiogenesis; Animals; Apoptosis; Ascites; Ascites - etiology; Ascites - therapy; Brain cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Chemotherapy; Coculture Techniques; Cytokines; Female; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - immunology; Interferon; Interferon-beta - metabolism; interferon‐β; iPS cell; Leukemia; macrophage; Macrophages; Metastases; Metastasis; Mice; Mice, SCID; Monocytes - cytology; Monocytes - immunology; Monocytes - transplantation; Original; Ovarian cancer; Ovarian Neoplasms - complications; Ovarian Neoplasms - immunology; Ovarian Neoplasms - therapy; Patients; peritoneal dissemination; Peritoneal Neoplasms - complications; Peritoneal Neoplasms - immunology; Peritoneal Neoplasms - therapy; Peritoneum; Pluripotency; Quality of life; Spheroids; Stem cells; Treatment Outcome; Tumor necrosis factor-TNF; Tumors; Xenograft Model Antitumor Assays; United States > US; macrophage; peritoneal dissemination; interferon-β; ovarian cancer; iPS cell
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13775

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.
Therapy based on the interaction of macrophages and ovarian cancer cells was tested. Induced pluripotent stem cell‐derived myelomonocytic cells producing interferon‐beta (iPS‐ML/IFN‐β) were used. iPS‐ML/IFN‐β coaggregated with ovarian cancer cells in vitro. iPS‐ML/IFN‐β therapy was effective against ovarian cancer in a xenograft model.