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Table of Contents
Vol. 23, No. 6, 2002
Issue release date: April 2003
Section title: Research Article
Tumor Biol 2002;23:337–347
(DOI:10.1159/000069793)

Targeting of Human Breast Cancer by a Bispecific Antibody Directed against Two Tumour-Associated Antigens: ErbB-2 and Carcinoembryonic Antigen

Dorvillius M.a · Garambois V.a · Pourquier D.b · Gutowski M.c · Rouanet P.c · Mani J.-C.d · Pugnière M.d · Hynes N.E.e · Pèlegrin A.a
aEMI 0227 INSERM and GDR CNRS 2352, Université Montpellier I, Cancer Research Centre, Departments of bPathology, Cancer Institute Val d’Aurelle-Paul Lamarque, cOncologic and Reconstructive Surgery, and dCentre National de la Recherche Scientifique, Unité Mixte de Recherche 5094, Faculty of Pharmacy, Montpellier, France; eFriedrich Miescher Institute, Basel, Switzerland

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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: October 17, 2002
Accepted: January 13, 2003
Published online: April 04, 2003
Issue release date: April 2003

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 3

ISSN: 1010-4283 (Print)
eISSN: 1423-0380 (Online)

For additional information: http://www.karger.com/TBI

Abstract

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 × 10 and 0.8 × 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 125I-BAb was lower than that of 131I-35A7F(ab′)2-PDM in LS174T tumours, used as a model of CEA expressing tumours, and was similar to that of 131I-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.

© 2002 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: October 17, 2002
Accepted: January 13, 2003
Published online: April 04, 2003
Issue release date: April 2003

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 3

ISSN: 1010-4283 (Print)
eISSN: 1423-0380 (Online)

For additional information: http://www.karger.com/TBI


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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