KRN7000, a novel immunomodulator, and its antitumor activities.
KRN7000, a compound with a novel alpha-galactosylceramide structure, showed potent tumor growth inhibitory activities in B16-bearing mice and markedly stimulated lymphocytic proliferation in allogeneic mixed leukocyte reaction, suggesting that KRN7000 is a biological response modifier. To confirm this suggestion, we examined the abilities of KRN7000 to enhance in vitro and in vivo natural killer (NK) activities, and found that KRN7000 enhanced in vitro and in vivo NK activities, and its potency on in vivo NK activity was much stronger than those of Poly I:C, which is a positive control, or the representative BRMs OK432 and Lentinan. In addition, since spleen cells intravenously treated with KRN7000 also showed potent cytotoxic activities against B16 and EL-4 cells, we evaluated the capability of KRN7000 to prolong the survival period of mice intravenously inoculated with B16 cells or mice intraperitoneally inoculated with EL-4 cells. In these models, KRN7000 (100 micrograms/kg) significantly prolonged the lifespan of mice, and its potency was stronger than that of Mitomycin C, a typical chemotherapeutic agent, in two models. These results demonstrate that KRN7000 would be a useful agent for cancer therapy.
Kobayashi
E
E
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Motoki
K
K
Uchida
T
T
Fukushima
H
H
Koezuka
Y
Y
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016685:Mitomycin / Q000494:pharmacology; D010844:Picibanil / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D013268:Stimulation, Chemical
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D005699:Galactosylceramides; D007155:Immunologic Factors; D010844:Picibanil; D016685:Mitomycin; D011070:Poly I-C; C103873:KRN 7000