Llama single-domain antibodies directed against nonconventional epitopes of tumor-associated carcinoembryonic antigen absent from nonspecific cross-reacting antigen

Autor: Daniel Baty, Amélie Cornillon, Martine Pugnière, Ghislaine Behar, Isabelle Teulon, Anne Gruaz-Guyon, Françoise Roquet, Jean-Luc Teillaud, Patrick Chames, Faisal Al-Shoukr, André Pèlegrin
Přispěvatelé: Unité de Biotechnologie, Biocatalyse et Biorégulation (U3B), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
Phage display
medicine.medical_treatment
Molecular Sequence Data
Mice
Nude
Cross Reactions
Immunofluorescence
Biochemistry
Antibodies
Epitope
Flow cytometry
Epitopes
Mice
03 medical and health sciences
0302 clinical medicine
Carcinoembryonic antigen
Antigen
Antibody Specificity
Cell Line
Tumor
Neoplasms
medicine
Animals
Humans
Amino Acid Sequence
Molecular Biology
030304 developmental biology
0303 health sciences
medicine.diagnostic_test
biology
Chemistry
Cell Biology
Immunotherapy
Surface Plasmon Resonance
Flow Cytometry
Xenograft Model Antitumor Assays
Molecular biology
Carcinoembryonic Antigen
3. Good health
030220 oncology & carcinogenesis
biology.protein
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Antibody
[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Camelids
New World
Sequence Alignment
Zdroj: FEBS Journal
FEBS Journal, 2009, 276 (14), pp.3881-93. ⟨10.1111/j.1742-4658.2009.07101.x⟩
FEBS Journal, Wiley, 2009, 276 (14), pp.3881-93. ⟨10.1111/j.1742-4658.2009.07101.x⟩
FEBS Journal, Wiley, 2009, june (00), pp.00
ISSN: 1742-464X
1742-4658
DOI: 10.1111/j.1742-4658.2009.07101.x⟩
Popis: International audience; Single-domain antibodies (sdAbs), which occur naturally in camelids, are endowed with many characteristics that make them attractive candidates as building blocks to create new antibody-related therapeutic molecules. In this study, we isolated from an immunized llama several high-affinity sdAbs directed against human carcinoembryonic antigen (CEA), a heavily glycosylated tumor-associated molecule expressed in a variety of cancers. These llama sdAbs bind a different epitope from those defined by current murine mAbs, as shown by binding competition experiments using immunofluorescence and surface plasmon resonance. Flow cytometry analysis shows that they bind strongly to CEA-positive tumor cells but show no cross-reaction toward nonspecific cross-reacting antigen, a highly CEA-related molecule expressed on human granulocytes. When injected into mice xenografted with a human CEA-positive tumor, up to 2% of the injected dose of one of these sdAbs was found in the tumor, despite rapid clearance of this 15 kDa protein, demonstrating its high potential as a targeting moiety. The single-domain nature of these new anti-CEA IgG fragments should facilitate the design of new molecules for immunotherapy or diagnosis of CEA-positive tumors.
Databáze: OpenAIRE
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