Potential for interferon-alpha-based therapy in mesothelioma: assessment in a murine model.
Malignant mesothelioma is an aggressive tumor, usually induced by asbestos exposure, that has a poor prognosis and is unresponsive to conventional therapy. The present study was aimed at assessing the potential for interferon-alpha (IFN-alpha)-based therapies in a murine model for malignant mesothelioma. The effect of recombinant human IFN-alpha B/D on tumor growth, alone and in combination with either of two immunomodulatory and antiproliferative agents beta-carotene or alpha-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN-alpha treatment is most efficacious when commenced early in tumor development. Combination of IFN-alpha with either DFMO or dietary beta-carotene supplementation improved the effect of an otherwise suboptimal IFN-alpha therapy regimen. Both IFN-alpha and beta-carotene had in vivo stimulatory effects on immune cells, perhaps indirectly by inhibiting TGF-beta generation. The immunomodulatory effects may contribute, at least in part, to the positive antitumor and clinical activities of the treatments in this model.
Bielefeldt-Ohmann
H
H
University of Western Australia Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands.
Fitzpatrick
D R
DR
Marzo
A L
AL
Jarnicki
A G
AG
Musk
A W
AW
Robinson
B W
BW
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002338:Carotenoids / Q000008:administration & dosage / Q000627:therapeutic use; D000518:Eflornithine / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008654:Mesothelioma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019207:beta Carotene
D000276:Adjuvants, Immunologic; D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D019207:beta Carotene; D002338:Carotenoids; D000518:Eflornithine