PRODUCTION AND TUMOR-BINDING CHARACTERIZATION OF A CHIMERIC ANTI-CEA FAB EXPRESSED IN ESCHERICHIA-COLI

被引:27
作者
CHESTER, KA [1 ]
ROBSON, L [1 ]
KEEP, PA [1 ]
PEDLEY, RB [1 ]
BODEN, JA [1 ]
BOXER, GM [1 ]
HAWKINS, RE [1 ]
BEGENT, RHJ [1 ]
机构
[1] MRC CTR,CAMBRIDGE CB2 2QH,CAMBS,ENGLAND
关键词
D O I
10.1002/ijc.2910570113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A recombinant chimeric Fab (rcFab), with Fv derived from the monoclonal A5B7 antibody to carcinoembryonic antigen (CEA), and with human CHI and C kappa was doned into pUC 19 and expressed in Escherichia coli. rcFab (10 to 12 mg per litre) was produced in bacterial culture fluid, and functional purified rcFab was isolated by affinity chromatography (using antibody to human C kappa) and size-exclusion gel filtration. The rcFab did not show reduced affinity for CEA, and reacted with human colorectal tumours showing a typical anti-CEA pattern by immunocytochemistry; it was also stable after iodination. Biodistribution studies in nude mice bearing human tumour xenografts showed no toxicity and good tumour localization. Therapeutic ratios at early time points were better than those obtained with whole murine antibody. The results demonstrate that bacterially produced anti-CEA Fab is of use for tumour targeting.
引用
收藏
页码:67 / 72
页数:6
相关论文
共 23 条
  • [1] ESCHERICHIA-COLI SECRETION OF AN ACTIVE CHIMERIC ANTIBODY FRAGMENT
    BETTER, M
    CHANG, CP
    ROBINSON, RR
    HORWITZ, AH
    [J]. SCIENCE, 1988, 240 (4855) : 1041 - 1043
  • [2] POTENT ANTI-CD5 RICIN-A CHAIN IMMUNOCONJUGATES FROM BACTERIALLY PRODUCED FAB' AND F(AB')2
    BETTER, M
    BERNHARD, SL
    LEI, SP
    FISHWILD, DM
    LANE, JA
    CARROLL, SF
    HORWITZ, AH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) : 457 - 461
  • [3] MOLECULAR AND FUNCTIONAL-CHARACTERIZATION OF A FUSION PROTEIN SUITED FOR TUMOR SPECIFIC PRODRUG ACTIVATION
    BOSSLET, K
    CZECH, J
    LORENZ, P
    SEDLACEK, HH
    SCHUERMANN, M
    SEEMANN, G
    [J]. BRITISH JOURNAL OF CANCER, 1992, 65 (02) : 234 - 238
  • [4] FACTORS INFLUENCING VARIABILITY OF LOCALIZATION OF ANTIBODIES TO CARCINOEMBRYONIC ANTIGEN (CEA) IN PATIENTS WITH COLORECTAL-CARCINOMA - IMPLICATIONS FOR RADIOIMMUNOTHERAPY
    BOXER, GM
    BEGENT, RHJ
    KELLY, AMB
    SOUTHALL, PJ
    BLAIR, SB
    THEODOROU, NA
    DAWSON, PM
    LEDERMANN, JA
    [J]. BRITISH JOURNAL OF CANCER, 1992, 65 (06) : 825 - 831
  • [5] BURNETTE WN, 1981, ANAL BIOCHEM, V112, P195, DOI 10.1016/0003-2697(81)90281-5
  • [6] INSITU AND SLOT HYBRIDIZATION ANALYSIS OF RNA IN COLORECTAL TUMORS AND NORMAL COLON SHOWS DISTINCT DISTRIBUTIONS OF MITOCHONDRIAL SEQUENCES
    CHESTER, KA
    ROBSON, L
    BEGENT, RHJ
    PRINGLE, H
    PRIMROSE, L
    TALBOT, IC
    MACPHERSON, AJS
    OWEN, SL
    BOXER, G
    MALCOLM, ADB
    [J]. JOURNAL OF PATHOLOGY, 1990, 162 (04) : 309 - 315
  • [7] GOLDENBERG DM, 1993, J NUCL MED, V34, P61
  • [8] SELECTION OF PHAGE ANTIBODIES BY BINDING-AFFINITY - MIMICKING AFFINITY MATURATION
    HAWKINS, RE
    RUSSELL, SJ
    WINTER, G
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1992, 226 (03) : 889 - 896
  • [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