Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-4-4
pubmed:abstractText
Carcinoembryonic antigen (CEA) and ErbB-2 are expressed in about 50 and 30% of breast cancers, respectively. We hypothesised that targeting of these two antigens by a bispecific antibody (BAb) might provide efficient tumour uptake and prolonged tumour residence time. In the present study, we first studied the expression of CEA and ErbB-2 on primary breast tumours screened by immunohistochemistry. Of 106 primary breast cancers, 69 (65%) were positive for CEA, 20 (19%) were positive for ErbB-2, and 13 (12%) expressed both antigens. We then prepared and evaluated a BAb directed against CEA and ErbB-2. Using BIACORE technology, we showed that the BAb recognised both CEA and ErbB-2 with affinities of 0.9 x 10 and 0.8 x 10 M(-1), respectively. In vivo, BAb tumour localisation was compared with that of its parental homodimeric F(ab')(2)-ORTHO-phenylene- dimaleimide (PDM) fragments. Uptake of (125)I-BAb was lower than that of (131)I-35A7F(ab')(2)-PDM in LS174T tumours, used as a model of CEA expressing tumours, and was similar to that of (131)I-FWP51 F(ab')(2)-PDM in SKOv3 tumours, used as a model of ErbB-2 expressing tumours. In a double-positive model, the SKOv3-CEA-1B9 tumour, BAb showed a similar uptake to that of 35A7 F(ab')(2)-PDM and we demonstrated that, although BAb had double specificity, it internalised as a homodimeric anti-ErbB-2 antibody. BAb showed a greater uptake than that of FWP51 F(ab')(2)-PDM and this difference was even more important 72 h after injection with an uptake of 7.3 +/- 2.1 vs. 1.4 +/- 0.5% of the injected dose per gram of tissue. The results obtained with the BAb in the double-positive tumour-bearing nude mice suggest that targeting two distinct tumour-associated antigens on the same cell could improve tumour localisation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1010-4283
pubmed:author
pubmed:copyrightInfo
Copyright 2002 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-47
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12677091-Adenocarcinoma, pubmed-meshheading:12677091-Adult, pubmed-meshheading:12677091-Aged, pubmed-meshheading:12677091-Aged, 80 and over, pubmed-meshheading:12677091-Animals, pubmed-meshheading:12677091-Antibodies, Bispecific, pubmed-meshheading:12677091-Antibodies, Neoplasm, pubmed-meshheading:12677091-Antibody Affinity, pubmed-meshheading:12677091-Antibody Specificity, pubmed-meshheading:12677091-Antigen-Antibody Reactions, pubmed-meshheading:12677091-Antigens, Neoplasm, pubmed-meshheading:12677091-Breast Neoplasms, pubmed-meshheading:12677091-Carcinoembryonic Antigen, pubmed-meshheading:12677091-Carcinoma, Ductal, Breast, pubmed-meshheading:12677091-Carcinoma, Lobular, pubmed-meshheading:12677091-Colonic Neoplasms, pubmed-meshheading:12677091-Drug Delivery Systems, pubmed-meshheading:12677091-Female, pubmed-meshheading:12677091-Flow Cytometry, pubmed-meshheading:12677091-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:12677091-Humans, pubmed-meshheading:12677091-Immunoglobulin Fab Fragments, pubmed-meshheading:12677091-Immunotherapy, pubmed-meshheading:12677091-Mice, pubmed-meshheading:12677091-Mice, Nude, pubmed-meshheading:12677091-Middle Aged, pubmed-meshheading:12677091-Neoplasm Proteins, pubmed-meshheading:12677091-Ovarian Neoplasms, pubmed-meshheading:12677091-Receptor, erbB-2, pubmed-meshheading:12677091-Surface Plasmon Resonance, pubmed-meshheading:12677091-Tissue Distribution, pubmed-meshheading:12677091-Transfection, pubmed-meshheading:12677091-Tumor Cells, Cultured, pubmed-meshheading:12677091-Tumor Markers, Biological, pubmed-meshheading:12677091-Xenograft Model Antitumor Assays
pubmed:articleTitle
Targeting of human breast cancer by a bispecific antibody directed against two tumour-associated antigens: ErbB-2 and carcinoembryonic antigen.
pubmed:affiliation
EMI 0227 INSERM and GDR CNRS 2352, Université Montpellier I, Cancer Research Centre, Montpellier, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't