Correlation of the antiproliferative effect and the Mx-homologous protein induction by IFN in patients with malignant melanoma.
The human interferon-induced intracellular protein homologous to the murine Mx-protein has recently been identified by means of a specific monoclonal antibody. Three of six melanoma cell lines elicited this intracellular human Mx-homolog upon incubation with IFN-alpha or IFN-gamma, yet all six melanoma cell lines tested were susceptible to the antiproliferative effect of IFN-alpha and IFN-gamma. Compared per antiviral unit, IFN-gamma had weaker Mx-inducing but stronger antiproliferative activity than IFN-alpha. These data suggest that the IFN-induced Mx-homologous protein is not involved in the antiproliferative action of IFN on malignant melanoma cell lines. Furthermore, 51 patients with advanced malignant melanoma were treated thrice weekly with 10 x 10(6) IU rIFN-alpha-2b and 6 x 10(6) nIFN-alpha, respectively. Nine of the 51 patients experienced systemic objective tumor responses (3 complete response, 6 partial response), but had Mx concentrations in their mononuclear cells equal to the Mx levels of non-responders during IFN-alpha therapy. Therefore, the level of Mx-homologous protein induced during IFN therapy is not a predictive marker for an antitumor response in malignant melanoma.
Jakschies
D
D
Department of Immunology and Transfusion Medicine, Medical School, Hannover, Germany.
Hochkeppel
H K
HK
Horisberger
M A
MA
Deicher
H
H
von Wussow
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D019204:GTP-Binding Proteins; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D007371:Interferon-gamma; D007372:Interferons; D019204:GTP-Binding Proteins