Characterization and humanization of a monoclonal antibody that neutralizes human leukocyte interferon: A candidate therapeutic for IDDM and SLE

被引:27
作者
Chuntharapai, A
Lai, J
Huang, XJ
Gibbs, V
Kim, KJ
Presta, LG
Stewart, TA
机构
[1] Genentech Inc, Dept Antibody Technol, San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA
[3] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA
[4] Genentech Inc, Dept Endocrinol, San Francisco, CA 94080 USA
关键词
D O I
10.1006/cyto.2001.0934
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2001 Academic Press.
引用
收藏
页码:250 / 260
页数:11
相关论文
共 80 条
[1]  
BALDINI L, 1986, BLOOD, V67, P458
[2]  
Baselga J, 1999, SEMIN ONCOL, V26, P78
[3]   Metal binding properties of a monoclonal antibody directed toward metal-chelate complexes [J].
Blake, DA ;
Chakrabarti, P ;
Khosraviani, M ;
Hatcher, FM ;
Westhoff, CM ;
Goebel, P ;
Wylie, DE ;
Blake, RC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27677-27685
[4]  
Caron PC, 1998, CLIN CANCER RES, V4, P1421
[5]   HUMANIZATION OF AN ANTI-P185HER2 ANTIBODY FOR HUMAN CANCER-THERAPY [J].
CARTER, P ;
PRESTA, L ;
GORMAN, CM ;
RIDGWAY, JBB ;
HENNER, D ;
WONG, WLT ;
ROWLAND, AM ;
KOTTS, C ;
CARVER, ME ;
SHEPARD, HM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4285-4289
[6]   Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia [J].
Chakrabarti, D ;
Huang, XJ ;
Beck, J ;
Henrich, J ;
McFarland, N ;
James, RFL ;
Stewart, TA .
DIABETES, 1996, 45 (10) :1336-1343
[7]  
Chakrabarti D, 1996, J IMMUNOL, V157, P522
[8]   CONFORMATIONS OF IMMUNOGLOBULIN HYPERVARIABLE REGIONS [J].
CHOTHIA, C ;
LESK, AM ;
TRAMONTANO, A ;
LEVITT, M ;
SMITHGILL, SJ ;
AIR, G ;
SHERIFF, S ;
PADLAN, EA ;
DAVIES, D ;
TULIP, WR ;
COLMAN, PM ;
SPINELLI, S ;
ALZARI, PM ;
POLJAK, RJ .
NATURE, 1989, 342 (6252) :877-883
[9]  
CONLON KC, 1990, CANCER, V65, P2237, DOI 10.1002/1097-0142(19900515)65:10<2237::AID-CNCR2820651013>3.0.CO
[10]  
2-5