In vitro inhibition of interferon alpha-2a antiproliferative activity by antibodies developed during treatment for essential thrombocythaemia.
BACKGROUND
Various authors have reported the development of anti-interferon (IFN) antibodies following IFN-alpha treatment for haematological malignancies. So far the methods for detecting these antibodies have not considered the antiproliferative activity of this IFN, which is its most important property in anticancer therapy.


METHODS
In this in vitro study we evaluated the ability of anti-IFN alpha-2a neutralising antibodies to inhibit the antiproliferative activity of IFN alpha-2a and lymphoblastoid IFN alpha using megakaryocyte colony growth as the revelatory system. These antibodies were detected in two patients affected by essential thrombocythaemia (ET) who lost their haematological response to IFN alpha-2a, but responded to a subsequent treatment with lymphoblastoid IFN alpha.


CONCLUSIONS
The results show that the inhibition of megakaryocyte colony growth induced by IFN alpha-2a was totally suppressed in the presence of the two ET patients' sera, whereas the inhibition induced by lymphoblastoid IFN alpha was not significantly affected. These in vitro data demonstrate the high specificity and activity of these antibodies on the antiproliferative effect of IFN alpha-2a.
Catani
L
L
Istituto di Ematologia L. & A. Seràgnoli, Università di Bologna, Italy.
Gugliotta
L
L
Zauli
G
G
Bagnara
G P
GP
Antonelli
G
G
Belmonte
M M
MM
Vianelli
N
N
Bonsi
L
L
Brunelli
M A
MA
Tura
S
S
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008533:Megakaryocytes / Q000187:drug effects; D009500:Neutralization Tests; D011994:Recombinant Proteins; D013920:Thrombocythemia, Essential / Q000276:immunology / Q000628:therapy*
D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007518:Isoantibodies; D011994:Recombinant Proteins