Therapy of primary and metastatic liver cancer by human iPS cell-derived myeloid cells producing interferon-[beta]

• Published in: Journal of hepato-biliary-pancreatic sciences Vol. 24; no. 2; p. 109
• Main Authors: Sakisaka, Masataka, Haruta, Miwa, Komohara, Yoshihiro, Umemoto, Satoshi, Matsumura, Keiko, Ikeda, Tokunori, Takeya, Motohiro, Inomata, Yukihiro, Nishimura, Yasuharu, Senju, Satoru
• Format: Journal Article
• Language: English
• Published: Tokyo Wiley Subscription Services, Inc 01.02.2017
• Subjects: Liver cancer; Metastasis; Rodents
• ISSN: 1868-6974; 1868-6982
• DOI: 10.1002/jhbp.422

Background iPS-ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem (iPS) cells. This study aimed to examine therapeutic effect of iPS-ML producing interferon-[beta] (iPS-ML/IFN-[beta]) towards primary and metastatic liver cancer and investigate the mechanism of that effect. Methods We established a xenograft model of liver metastasis by injecting the spleen of SCID mice with MKN-45 human gastric cancer cells and also a primary liver cancer model by injecting SK-HEP-1 human hepatocellular carcinoma cells into the liver. After cancer lesions were established, iPS-ML/IFN-[beta] was administered by intraperitoneal injection, and therapeutic effect was evaluated. Results The i.p. injection of iPS-ML/IFN-[beta] resulted in a significant retardation of cancer progression and prolonged mouse survival. The infiltration of i.p. administered iPS-ML into tumor lesions located below the liver capsule was observed, suggesting tumor-directed migration and penetration of the liver capsule by iPS-ML. The IFN-[beta] concentration in the liver was maintained at levels sufficient to exert an anti-cancer effect for at least 3 days post-injection, accounting for the potent therapeutic effect obtained by injection two to three times per week. Conclusions This study demonstrates the therapeutic potential of the iPS-ML/IFN-[beta] in patients with liver cancer.