Neutralizing interferon beta antibodies in melanoma patients treated with recombinant and natural interferon beta

The incidence and clinical significance of therapy-induced neutralizing interferon beta (IFN beta) antibodies was studied in a group of 21 melanoma patients treated with natural IFN beta and 7 patients treated with recombinant IFN beta. They were treated subcutaneously with 3 x 10(6) IU three times per week in an adjuvant open trial for 24 weeks after surgical removal of all detectable metastases. Of the 21 patients treated with natural IFN beta, 95% developed significant levels of neutralizing antibodies after 24 weeks. In comparison, 28% of the 7 patients treated with recombinant IFN beta developed neutralizing IFN beta antibodies. Cross-reactivity of the antibodies could be demonstrated. Persistence of antibody titers was seen in 80% of the patients 24 weeks after cessation of treatment with natural IFN beta. No correlation between the maximum antibody titers and the antibody persistence after cessation of therapy could be established. We detected a clear correlation between the formation of neutralizing antibodies and the decrease in beta 2-microglobulin and 2',5'-oligoadenylate synthetase and therefore the drop in biological activity. In this adjuvant trial there was no difference in relapse rate and time until relapse between antibody-positive and antibody-negative patients. No difference in clinical outcome could be established between the patients treated with natural IFN beta and recombinant IFN beta.