Masataka Sakisaka1,2, Miwa Haruta3, Yoshihiro Komohara4, Satoshi Umemoto3, Keiko Matsumura3, Tokunori Ikeda3, Motohiro Takeya4, Yukihiro Inomata2, Yasuharu Nishimura3, Satoru Senju3. 1. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 2. Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 3. Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. 4. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Abstract
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-β (iPS-ML/IFN-β) 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-β was administered by intraperitoneal injection, and therapeutic effect was evaluated. RESULTS: The i.p. injection of iPS-ML/IFN-β 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-β 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-β in patients with liver cancer.
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-β (iPS-ML/IFN-β) 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 SCIDmice with MKN-45humangastric cancer cells and also a primary liver cancer model by injecting SK-HEP-1 humanhepatocellular carcinoma cells into the liver. After cancer lesions were established, iPS-ML/IFN-β was administered by intraperitoneal injection, and therapeutic effect was evaluated. RESULTS: The i.p. injection of iPS-ML/IFN-β 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-β 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-β in patients with liver cancer.