Interferons (IFN-alpha, IFN-beta, and IFN-gamma) are natural host proteins which have antiviral, immunoregulatory, and antiproliferative activities. A number of clinical trials have examined interferons for their clinical potential. Unfortunately, while they have shown real promise for the control of certain types of cancer, they have been limited in their effectiveness and have not been found to be highly potent against most of the types of cancers tested. Further, interferon therapy has a number of side effects, including bone marrow suppression. A major challenge is to increase the antitumor activity of the interferons while reducing or moderating their side effects. This proposal focuses on this challenge by 1) evaluating combined interferon treatment (IFN-gamma plus either IFN-alpha or IFN-beta) in various treatment protocols as a means of maximizing interferon activity; 2) evaluating the combined effects of colony stimulating factors and other myeloregulatory agents as a means of minimizing the bone marrow suppressive effect of interferon therapy; 3) removing an inhibitor of interferon action from IFN- gamma preparations as a means of maximizing IFN-gamma activity; and, 4) evaluating the combined effects of antitumor drugs and interferons as a means of maximizing their antitumor activities. The proposed research seeks to investigate basic mechanisms, while providing important insights for the clinical application of interferon.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026475-09
Application #
3167329
Study Section
Experimental Immunology Study Section (EI)
Project Start
1983-12-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1990-11-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Fleischmann, C M; Fleischmann Jr, W R (1991) Resistance to the antiproliferative activity of IFN-alpha: further characterization and demonstration of antagonistic effects of IFN-gamma. J Biol Regul Homeost Agents 5:34-42
Fleischmann Jr, W R; Fields, E E; Wang, J L et al. (1991) Modulation of peripheral leukocyte counts in mice by oral administration of interferons. Proc Soc Exp Biol Med 197:424-30
Kotnik, V; Fleischmann Jr, W R (1990) A simple and rapid method to determine hematopoietic growth factor activity. J Immunol Methods 129:23-30
Fleischmann Jr, W R; Ramarathinam, N; Fields, E E (1990) Effects of phenytoin on the production of interferons: differential effects on type I and type II interferons. J Biol Regul Homeost Agents 4:107-16
Fleischmann, C M; Fleischmann Jr, W R (1988) Effects of hyperthermia on the in vitro antiproliferative activities of HuIFN-alpha, HuIFN-beta, and rHuIFN-gamma employed separately and in combination. J Biol Regul Homeost Agents 2:145-54
Fleischmann, C M; Fleischmann Jr, W R (1988) Differential antiproliferative activities of IFNs alpha, beta and gamma: kinetics of establishment of their antiproliferative effects and the rapid development of resistance to IFNs alpha and beta. J Biol Regul Homeost Agents 2:173-85
Ramamurthy, V; Fleischmann Jr, W R (1988) Regulation of MuIFN-alpha/beta and MuIFN-gamma-induced antiviral states: differential effects with different challenge viruses and lack of correlation with 2'5' oligoadenylate synthetase levels. J Biol Regul Homeost Agents 2:7-14
Naldini, A; Fleischmann Jr, W R (1987) In vivo myelosuppression by combination interferon treatment: antagonism of MuIFN-gamma and MuIFN-beta myelosuppressive effects. J Biol Response Mod 6:546-55
Naldini, A; Fleischmann Jr, W R; Ballas, Z K et al. (1987) Interleukin 2 inhibits in vitro granulocyte-macrophage colony formation. J Immunol 139:1880-4
Koren, S; Fleischmann Jr, W R (1986) Quantitation of in vivo potentiation resulting from combined interferon therapy: antitumor effect against B-16 melanoma in mice. J Interferon Res 6:473-82

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