Characterization of anti-interferon-alpha antibodies appearing during recombinant interferon-alpha 2a treatment.
Patients with malignant midgut carcinoid tumours received recombinant interferon-alpha 2a (rIFN-alpha 2a) or rIFN-alpha 2a and chemotherapy (streptozocin and doxorubicin) for 6 months, and then rIFN-alpha 2a alone. Antibodies, mainly of IgG type, binding to rIFN-alpha 2a developed in nine of 22 patients (41%), as determined by immunoassay. In seven patients, antibodies also neutralized the biologic (anti-viral) activity of rIFN-alpha 2a. Anti-IFN-alpha 2a 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-alpha 2a treatment and had a median duration of 6 months. The anti-IFN-alpha 2a antibody titres declined with time with no obvious relation to change of therapy, also during continued IFN-alpha 2a treatment. High titres of neutralizing antibodies appeared to impair anti-tumoural effects in individual potential responders. Anti-IFN-alpha 2a antibodies further examined in six patients bound to native IFN-alpha subtypes present in both allogenic and autologous leucocyte IFN-alpha. Such autoantibodies neutralized the biologic activity of autologous IFN-alpha in two patients, and in a third were partially neutralizing.
Rönnblom
L E
LE
Department of Internal Medicine, Central Hospital, Boden, Sweden.
Janson
E T
ET
Perers
A
A
Oberg
K E
KE
Alm
G V
GV
D000368:Aged; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D000917:Antibody Formation; D002276:Carcinoid Tumor / Q000188:drug therapy; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
D000906:Antibodies; D007132:Immunoglobulin Isotypes; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins