Immunotherapy with low-dose interleukin-2 and interferon-gamma in a murine tumor model.
The aim of this study was to evaluate the therapeutic efficacy of locally administered low-dose interleukin-2 (IL-2) alone or together with interferon-gamma (IFN-gamma) in a herpes simplex virus type 2-transformed murine (H238) fibrosarcoma model. In vitro incubation showed that IL-2, but not IFN-gamma, had a significant inhibitory effect on DNA synthesis in H238 cells. In vivo experiments were performed with BALB/c mice to determine the optimal time of treatment with each cytokine after subcutaneous (sc) tumor implantation. The greatest antitumor effect with IL-2 (1 x 10(5) total international units, sc) was noted when treatment was administered during the first week after tumor injection, whereas with IFN-gamma (500 total units, intraperitoneally) treatment during the second week proved best. Combination of the two agents produced complete tumor regression in 44.4% of mice; regression with single-modality treatment was 0-11%. The presence of H238 tumor induced splenomegaly and enhanced the oxidative burst capacity of phagocytes. Peripheral blood leukocyte counts were low in tumor-bearing groups, regardless of treatment. IL-2 and IFN-gamma were nondetectable in the plasma of tumor-bearing or control mice; however, total TGF-beta 1 was 248% higher with IL-2 treatment compared with tumor-bearing nontreated controls. These results show that IL-2 and IFN-gamma can significantly inhibit the growth of highly aggressive H238 tumors and support further investigations with these agents.
Mao
X W
XW
Department of Microbiology and Molecular Genetics, Loma Linda University School of Medicine, CA 92350, USA.
Kettering
J D
JD
Gridley
D S
DS
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D007371:Interferon-gamma / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma