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A Partially Humanized Monoclonal Antibody to Human IFN‐γ Inhibits Cytokine Effects both In Vitro and In Vivo
Author(s) -
Fiorentini S.,
De Panfilis G.,
Pasolini G.,
Bonfanti C.,
Caruso A.
Publication year - 2002
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2002.01039.x
Subject(s) - in vivo , monoclonal antibody , immunogenicity , cytokine , antibody , interferon , in vitro , immunology , biology , microbiology and biotechnology , virology , chemistry , biochemistry
The mouse monoclonal antibody (MoAb) IGMB17 (muIGMB17) is a high‐affinity antibody‐ neutralizing human interferon (IFN)‐γ and, accordingly, is a potential therapeutic agent for patients suffering from various diseases in which the cytokine is abnormally expressed. The clinical usefulness of mouse antibodies is limited, however, owing to their immunogenicity in humans. MuIGMB17 antibody was partially humanized by engrafting a small portion of mouse light chain (LC) in a human framework and by engineering its heavy chain (HC) in a chimeric version. The engineered IGMB17 (huIGMB17) was able to replicate a range of functional properties of the original muIGMB17, namely, specific binding to IFN‐γ, inhibition of histocompatibility complex (HLA‐DR) expression in response to IFN‐γ induction, reversion of IFN‐γ antiproliferative activity on sensitive cell lines. We have hypothesized that as huIGMB17 was able to block IFN‐γ binding to its receptor as well as its murine counterpart, huIGMB17 could neutralize all cytokine activity, also in vivo . Indeed huIGMB17 was capable of interfering with delayed‐type hypersensitivity reaction in humans, thus demonstrating its effectiveness in neutralizing IFN‐γ‐mediated reactions in vivo .