Antitumor effect of combination of murine recombinant interferon beta, murine recombinant interferon gamma and human recombinant interleukin-2 in MethA-bearing mice.
We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.
Itoh
T
T
First Department of Internal Medicine, Hirosaki University School of Medicine, Japan.
Sakata
Y
Y
Yoshida
Y
Y
Tsushima
K
K
Suzuki
H
H
Saitoh
S
S
Tamura
Y
Y
Ogasawara
H
H
Sugimoto
N
N
Takemori
H
H
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004334:Drug Administration Schedule; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage; D007371:Interferon-gamma / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma