Therapeutic antibody fragments with prolonged in vivo half-lives

被引:265
作者
Chapman, AP [1 ]
Antoniw, P [1 ]
Spitali, M [1 ]
West, S [1 ]
Stephens, S [1 ]
King, DJ [1 ]
机构
[1] Celltech Therapeut, Slough SL1 4EN, Berks, England
关键词
therapeutic antibodies; antibody engineering; polyethylene glycol; pharmacokinetics;
D O I
10.1038/11717
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Antibody fragments can be isolated rapidly using techniques such as phage display and can be expressed to high levels in microbial systems. However, to date such antibody fragments have been of limited use for many therapeutic applications because they are rapidly cleared from the body. We present a strategy for the site-specific chemical modification of antibody fragments with polyethylene glycol, which results in the production of antibody fragments with long in vivo half-lives and full retention of antigen-binding properties. This technology should allow more rapid and economical production of therapeutic antibodies for chronic disease therapy.
引用
收藏
页码:780 / 783
页数:4
相关论文
共 16 条
  • [1] HIGH-LEVEL EXPRESSION OF A RECOMBINANT ANTIBODY FROM MYELOMA CELLS USING A GLUTAMINE-SYNTHETASE GENE AS AN AMPLIFIABLE SELECTABLE MARKER
    BEBBINGTON, CR
    RENNER, G
    THOMSON, S
    KING, D
    ABRAMS, D
    YARRANTON, GT
    [J]. BIO-TECHNOLOGY, 1992, 10 (02): : 169 - 175
  • [2] HIGH-LEVEL ESCHERICHIA-COLI EXPRESSION AND PRODUCTION OF A BIVALENT HUMANIZED ANTIBODY FRAGMENT
    CARTER, P
    KELLEY, RF
    RODRIGUES, ML
    SNEDECOR, B
    COVARRUBIAS, M
    VELLIGAN, MD
    WONG, WLT
    ROWLAND, AM
    KOTTS, CE
    CARVER, ME
    YANG, M
    BOURELL, JH
    SHEPARD, HM
    HENNER, D
    [J]. BIO-TECHNOLOGY, 1992, 10 (02): : 163 - 167
  • [3] Cancer therapy - Antibodies stage a comeback in cancer treatment
    Dickman, S
    [J]. SCIENCE, 1998, 280 (5367) : 1196 - 1197
  • [4] RANDOMIZED DOUBLE-BLIND COMPARISON OF CHIMERIC MONOCLONAL-ANTIBODY TO TUMOR-NECROSIS-FACTOR-ALPHA (CA2) VERSUS PLACEBO IN RHEUMATOID-ARTHRITIS
    ELLIOTT, MJ
    MAINI, RN
    FELDMANN, M
    KALDEN, JR
    ANTONI, C
    SMOLEN, JS
    LEEB, B
    BREEDVELD, FC
    MACFARLANE, JD
    BIJL, H
    WOODY, JN
    [J]. LANCET, 1994, 344 (8930) : 1105 - 1110
  • [5] High volumetric yields of functional dimeric miniantibodies in Escherichia coli, using an optimized expression vector and high-cell-density fermentation under non-limited growth conditions
    Horn, U
    Strittmatter, W
    Krebber, A
    Knupfer, U
    Kujau, M
    Wenderoth, R
    Muller, K
    Matzku, S
    Pluckthun, A
    Riesenberg, D
    [J]. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 1996, 46 (5-6) : 524 - 532
  • [6] F(ab′)2 molecules made from Escherichia coli produced Fab′ with hinge sequences conferring increased serum survival in an animal model
    Humphreys, DP
    Vetterlein, OM
    Chapman, AP
    King, DJ
    Antoniw, P
    Suitters, AJ
    Reeks, DG
    Parton, TAH
    King, LM
    Smith, BJ
    Lang, V
    Stephens, PE
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1998, 217 (1-2) : 1 - 10
  • [7] KING DJ, 1994, CANCER RES, V54, P6176
  • [8] KING DJ, 1992, ANTIBODY IMMUNOCONJ, V5, P159
  • [9] KITAMURA K, 1991, CANCER RES, V51, P4310
  • [10] Stabilization of substances in circulation
    Monfardini, C
    Veronese, FM
    [J]. BIOCONJUGATE CHEMISTRY, 1998, 9 (04) : 418 - 450