Antitumor activities of combined treatment with a novel immunomodulator, (2S,3S,4R)-1-O-(alpha-D-Galactopyranosyl)-2-(N-Hexacosanoylamino)-1,3,4 - octadecanetriol (KRN7000), and radiotherapy in tumor-bearing mice.
The novel immunomodulator (2S,3S,4R)-I-O-(alpha-D-galactopyranosyl)-2- (N-hexacosanoylamino)-1,3,4-octadecanetriol (KRN7000) in combination with high-dose (20 and 30 Gy) local x-ray irradiation or low-dose (3 Gy) fractionated whole-body irradiation showed significantly stronger antitumor activities against Meth A-and Colon26-bearing mice than treatments by radiation or KRN7000 alone, and 60% of mice in combination treatment groups were cured. Furthermore, the results of tests rechallenging the cured mice with Meth A and Colon26 cells strongly suggested that tumor-specific immunity was induced by the combination treatment. The suggestion was supported by the result that the systemic administration of KRN7000 could produce large amounts of interleukin-2 and interferon-gamma, which contribute to induction of tumor-specific cytotoxic lymphocytes not only in normal mice but also in whole-body irradiated mice. Furthermore, it was also suggested that KRN7000 contributes to protecting antitumor effector cells, such as natural killer cells, from impairments caused by radiation. Taking together the results and the knowledge that tumor-specific cytotoxic lymphocytes play a critical role in prevention of tumor recurrence and distant metastasis, it is strongly suggested that combined therapy with KRN7000 and radiation could be quite useful for cancer treatment.
Motoki
K
K
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd. Gunma, Japan.
Maeda
K
K
Ueno
H
H
Kobayashi
E
E
Uchida
T
T
Fukushima
H
H
Koezuka
Y
Y
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D002277:Carcinoma / Q000532:radiotherapy / Q000628:therapy*; D003110:Colonic Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005699:Galactosylceramides / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000532:radiotherapy / Q000628:therapy*; D014916:Whole-Body Irradiation; D014964:X-Ray Therapy
D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; C103873:KRN 7000