Characterization of anti-interferon-α antibodies appearing during recombinant interferon-α2a treatment

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Abstract
SUMMARY: Patients with malignant midgut carcinoid tumours received recombinant interferon-alpha2a (rIFN-α2a) or rIFN-α2a and chemotherapy (streptozocin and doxorubicin) for 6 months, and then rIFN-α2a alone. Antibodies, mainly of IgG type, binding to rIFN-α2a developed in nine of 22 patients (41%), as determined by immunoassay. In seven patients, antibodies also neutralized the biologic (anti-viral) activity of rIFN-α2a. Anti-IFN-α2a antibodies were equally frequent in both sexes and treatment groups, but were not observed in those patients (n=8) that had previously received other types of IFN. Antibodies appeared after a median of 6 months of rIFN-α2a treatment and had a median duration of 6 months. The anti-IFN-α2a antibody titres declined with time with no obvious relation to change of therapy, also during continued IFN-α2a treatment. High titres of neutralizing antibodies appeared to impair anti-tumoural effects in individual potential responders. Anti-IFN-α2a antibodies further examined in six patients bound to native IFN-α subtypes present in both allogeneic and autologous leucocyte IFN-α. Such autoantibodies neutralized the biologic activity of autologous IFN-α in two patients, and in a third were partially neutralizing.