A POSSIBLE PROCEDURE FOR REDUCING THE IMMUNOGENICITY OF ANTIBODY VARIABLE DOMAINS WHILE PRESERVING THEIR LIGAND-BINDING PROPERTIES

被引:119
作者
PADLAN, EA
机构
[1] Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda
关键词
D O I
10.1016/0161-5890(91)90163-E
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
It is proposed to reduce the immunogenicity of allogeneic antibody variable domains, while preserving ligand-binding properties, by reducing their antigenicity through replacement of the exposed residues in the framework regions which differ from those usually found in host antibodies. The results of a comparison of representative murine antibody sequences with those of human origin suggest that the number of residues that need to be replaced to "humanize" those antibodies could be small.
引用
收藏
页码:489 / 498
页数:10
相关论文
共 23 条
  • [1] 3-DIMENSIONAL STRUCTURE OF AN ANTIGEN-ANTIBODY COMPLEX AT 2.8-A RESOLUTION
    AMIT, AG
    MARIUZZA, RA
    PHILLIPS, SEV
    POLJAK, RJ
    [J]. SCIENCE, 1986, 233 (4765) : 747 - 753
  • [2] THE ANTIGENIC STRUCTURE OF PROTEINS - A REAPPRAISAL
    BENJAMIN, DC
    BERZOFSKY, JA
    EAST, IJ
    GURD, FRN
    HANNUM, C
    LEACH, SJ
    MARGOLIASH, E
    MICHAEL, JG
    MILLER, A
    PRAGER, EM
    REICHLIN, M
    SERCARZ, EE
    SMITHGILL, SJ
    TODD, PE
    WILSON, AC
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1984, 2 : 67 - 101
  • [3] PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
    BERNSTEIN, FC
    KOETZLE, TF
    WILLIAMS, GJB
    MEYER, EF
    BRICE, MD
    RODGERS, JR
    KENNARD, O
    SHIMANOUCHI, T
    TASUMI, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1977, 112 (03) : 535 - 542
  • [4] DYNAMICS OF LIGAND-BINDING TO HEME-PROTEINS
    CASE, DA
    KARPLUS, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1979, 132 (03) : 343 - 368
  • [5] 3-DIMENSIONAL STRUCTURE OF A COMPLEX OF ANTIBODY WITH INFLUENZA-VIRUS NEURAMINIDASE
    COLMAN, PM
    LAVER, WG
    VARGHESE, JN
    BAKER, AT
    TULLOCH, PA
    AIR, GM
    WEBSTER, RG
    [J]. NATURE, 1987, 326 (6111) : 358 - 363
  • [6] ANALYTICAL MOLECULAR-SURFACE CALCULATION
    CONNOLLY, ML
    [J]. JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1983, 16 (OCT) : 548 - 558
  • [7] ANTIBODY-ANTIGEN COMPLEXES
    DAVIES, DR
    PADLAN, EA
    SHERIFF, S
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1990, 59 : 439 - 473
  • [8] GENERATION OF A LARGE COMBINATORIAL LIBRARY OF THE IMMUNOGLOBULIN REPERTOIRE IN PHAGE-LAMBDA
    HUSE, WD
    SASTRY, L
    IVERSON, SA
    KANG, AS
    ALTINGMEES, M
    BURTON, DR
    BENKOVIC, SJ
    LERNER, RA
    [J]. SCIENCE, 1989, 246 (4935) : 1275 - 1281
  • [9] REPLACING THE COMPLEMENTARITY-DETERMINING REGIONS IN A HUMAN-ANTIBODY WITH THOSE FROM A MOUSE
    JONES, PT
    DEAR, PH
    FOOTE, J
    NEUBERGER, MS
    WINTER, G
    [J]. NATURE, 1986, 321 (6069) : 522 - 525
  • [10] Kabat E. A., 1987, SEQUENCES PROTEINS I, DOI 10.1016/0003-2697(84)90805-4