Enhancement of MuIFN-gamma antitumor effects by hyperthermia: sequence dependence and time dependence of hyperthermia.
Heat-induced total body hyperthermia has been shown to synergistically enhance the in vivo antitumor effects of MuIFN-gamma directed against B16 melanoma in mice. This observation was made with an 8-hour exposure to hyperthermia that was administered following MuIFN-gamma treatment. It was not known whether this was the most efficacious treatment protocol. Various treatment protocols exploring MuIFN-gamma treatment at different relative times of exposure to hyperthermia and involving different durations of hyperthermia were evaluated. In a 5-day course of therapy, B16 tumor-bearing mice were injected with MuIFN-gamma or mock interferon and incubated in a dry incubator (resulting in a 2 degrees C rise in body temperature). The antitumor efficacy of MuIFN-gamma administered before, in the middle of, or following 8 hours of hyperthermia was evaluated. The antitumor effects of MuIFN-gamma were synergistically enhanced when the MuIFN-gamma was administered before 8 hours of hyperthermia (3.9-fold greater increased life span than with MuIFN-gamma treatment alone). However, when MuIFN-gamma was administered in the middle or following hyperthermia, the life spans were essentially the same as for MuIFN-gamma treatment alone, indicating that the effect of the hyperthermia exposures according to these treatment protocols were less than additive. Administration of MuIFN-gamma before hyperthermia exposures of 2 hours, 5 hours, and 8 hours showed antagonistic, additive, and synergistic interactions of the MuIFN-gamma treatment and hyperthermia exposure, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Fleischmann
W R
WR
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USA.
Fleischmann
C M
CM
D000818:Animals; D003131:Combined Modality Therapy; D005260:Female; D006979:Hyperthermia, Induced; D007371:Interferon-gamma / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D013997:Time Factors
D011994:Recombinant Proteins; D007371:Interferon-gamma