Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients.
In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.
Dummer
R
R
Department of Dermatology, University of Würzburg, Federal Republic of Germany.
Müller
W
W
Nestle
F
F
Wiede
J
J
Dues
J
J
Lechner
W
W
Haubitz
I
I
Wolf
W
W
Bill
E
E
Burg
G
G
D000906:Antibodies / Q000032:analysis*; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005121:Extremities; D006258:Head and Neck Neoplasms / Q000628:therapy; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007370:Interferon Type I / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D009500:Neutralization Tests; D015375:Receptors, Interleukin-2 / Q000097:blood; D011994:Recombinant Proteins
D000906:Antibodies; D007370:Interferon Type I; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma