Antitumor effect of whole body hyperthermia combined with alpha-galactosylceramide in subcutaneous tumor model of colon cancer

4424 Aim: Whole body hyperthermia (WBH) has been used clinically as an adjunct to radio-/chemotherapy in patients with various cancers. Recently, it has been reported that an activation of the immune system might contribute to the therapeutic effect of WBH. On the other hand, it has been established that alpha-galactosylceramide (alpha-GalCer), a glycolipid, is recognized by natural killer T (NKT) cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. In this study, we investigated the antitumor effect of WBH combined with alpha-GalCer in mouse subcutaneous tumor model of colon cancer. Methods: Colon26 cells were inoculated subcutaneously in male BALB/c mice to establish subcutaneous tumor. Colon26-bearing mice were treated with whole body hyperthermia by using far infrared rays 3 times a week. Rectal temperature was maintained for 60 min at 41 degrees Celsius. In some experimental groups, alpha-GalCer was intraperitoneally injected before WBH. We investigated the therapeutic effect of WBH, alpha-GalCer, and the combined therapy. Furthermore, we also investigated the mechanism of antitumor effect by monitoring the change of IFN-gamma, NK activity, CTL activity. Results: (1) Compared with control group, whole body hyperthermia alone showed a tendency to inhibit tumor growth and to prolong survival rate. (2) Alpha-GalCer did not show the inhibitory effect to tumor growth. (3) The combination of whole body hyperthermia and alpha-GalCer showed significant inhibitory effect of tumor growth and prolongation of survival rate. (4) Serum IFN-gamma increased after 3 hours and returned to its basal level after 24hours of alpha-GalCer administration. (5) Both NK activity and CTL activity were enhanced on the group of combination therapy with whole body hyperthermia and alpha-GalCer. Conclusion: (1) Whole body hyperthermia showed the antitumor effect on mouse subcutaneous tumor model of colon cancer. (2) The combination with alpha-GalCer increased the efficacy of whole body hyperthermia probably via the enhancement of both NK activity and CTL activity.