Characterization and humanization of a monoclonal antibody that neutralizes human leukocyte interferon: a candidate therapeutic for IDDM and SLE.
We have developed a panel of murine monoclonal antibodies that recognize human interferon alpha. One of these mononclonal antibodies binds and neutralizes, with high affinity, all of seven tested recombinant human interferon alphas. This mononclonal antibody also neutralizes the interferon activity present in two independent pools of interferon alphas prepared following stimulation of human peripheral blood leukocytes. The complementary determining regions from this murine mononclonal antibody were transferred to a human IgG2 heavy chain and to a human kappa1 light chain. In addition, six (heavy chain) and two (light chain) amino acids were transferred from the framework regions. This generated a humanized mononclonal antibody that retained the specificity of the mouse parent. The humanized anti-interferon alpha antibody is a candidate therapeutic for those diseases, such as insulin-dependent diabetes, systemic lupus erythematosis, psoriasis and Crohn's disease, which are all characterized by pathological expression of interferon alpha.
Chuntharapai
A
A
Department of Antibody Technology, Genentech, South San Francisco, CA 94080, USA.
Lai
J
J
Huang
X
X
Gibbs
V
V
Kim
K J
KJ
Presta
L G
LG
Stewart
T A
TA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use*; D015374:Biosensing Techniques; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D016898:Interferon-alpha / Q000737:chemistry* / Q000276:immunology; D016899:Interferon-beta / Q000737:chemistry / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016899:Interferon-beta