Efficacy and toxicity elicited by recombinant interferons alpha and gamma when administered in combination to tumor-bearing mice.
Administration of rHuIFN-alpha A/D and rMuIFN-gamma as single agents to tumor-bearing mice resulted in a dose-related antitumor effect in each of the six models studied. When the IFNs were given in combination, the effects varied between the tumor systems. No increase in efficacy was seen in mice bearing B16-F10 melanoma or M5076 reticulum cell sarcoma while additive antitumor activity was shown in the KA31 fibrosarcoma and P388 leukemia systems. Mice inoculated with L1210 lymphoma or colon 38 carcinoma, however, revealed enhanced efficacy which was greater than additive. The data also reveal that combination of IFNs alpha and gamma administered to normal and tumor-bearing mice resulted in toxicity which was not predicted by the appropriate doses of the single agents. These studies suggest that combination of IFNs alpha and gamma may provide greater therapeutic utility than the single agents and underscore the need for additional, carefully designed preclinical and clinical efforts.
Truitt
G A
GA
Department of Oncology and Virology, Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Bontempo
J M
JM
Stern
L L
LL
Sulich
V
V
Bellantoni
D
D
Trown
P W
PW
Brunda
M J
MJ
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D007370:Interferon Type I / Q000008:administration & dosage* / Q000633:toxicity; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000628:therapy*; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma