Generation and characterization of recombinant human antibodies specific for native laminin epitopes: Potential application in cancer therapy

Laura Sanz, Peter Kristensen, Stephen J Russell, Jose Ramirez García, Luis Álvarez-Vallina

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Laminins are specific cellular regulators that directly and indirectly control activities such as cell attachment and migration, differentiation and polarity, proliferation and apoptosis, and protease expression. Considering the centrality of these issues to tumor progression, the generation of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library of single chain antibodies was selected using intact mouse laminin, and five different clones were identified. All the antibodies were specific for their cognate antigen, as revealed by lack of cross-reactivity with other components of the basement membranes. A more extensive characterization of the panel indicated that these antibodies recognize the native protein through conformational epitopes. All of them reduced tumor cell attachment to laminin, suggesting that domains of the laminin molecule that are recognized by these antibodies likely bind to cell-surface receptors. The antibody fragments bind to mouse, rat and human laminin, and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications.

Original languageEnglish (US)
Pages (from-to)557-565
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume50
Issue number10
DOIs
StatePublished - 2001

Fingerprint

Laminin
Epitopes
Antibodies
Immunoglobulin Fragments
Neoplasms
Basement Membrane
Therapeutics
Single-Chain Antibodies
Cell Polarity
Cell Surface Receptors
Bacteriophages
Cell Movement
Anti-Idiotypic Antibodies
Peptide Hydrolases
Clone Cells
Apoptosis
Technology
Antigens
Proteins

Keywords

  • Cancer
  • Extracellular matrix
  • Human antibodies
  • Laminin
  • Phage display

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Generation and characterization of recombinant human antibodies specific for native laminin epitopes : Potential application in cancer therapy. / Sanz, Laura; Kristensen, Peter; Russell, Stephen J; Ramirez García, Jose; Álvarez-Vallina, Luis.

In: Cancer Immunology, Immunotherapy, Vol. 50, No. 10, 2001, p. 557-565.

Research output: Contribution to journalArticle

@article{bb9f03a93abf4cc7957a9324354d8f37,
title = "Generation and characterization of recombinant human antibodies specific for native laminin epitopes: Potential application in cancer therapy",
abstract = "Laminins are specific cellular regulators that directly and indirectly control activities such as cell attachment and migration, differentiation and polarity, proliferation and apoptosis, and protease expression. Considering the centrality of these issues to tumor progression, the generation of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library of single chain antibodies was selected using intact mouse laminin, and five different clones were identified. All the antibodies were specific for their cognate antigen, as revealed by lack of cross-reactivity with other components of the basement membranes. A more extensive characterization of the panel indicated that these antibodies recognize the native protein through conformational epitopes. All of them reduced tumor cell attachment to laminin, suggesting that domains of the laminin molecule that are recognized by these antibodies likely bind to cell-surface receptors. The antibody fragments bind to mouse, rat and human laminin, and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications.",
keywords = "Cancer, Extracellular matrix, Human antibodies, Laminin, Phage display",
author = "Laura Sanz and Peter Kristensen and Russell, {Stephen J} and {Ramirez Garc{\'i}a}, Jose and Luis {\'A}lvarez-Vallina",
year = "2001",
doi = "10.1007/s00262-001-0235-5",
language = "English (US)",
volume = "50",
pages = "557--565",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "10",

}

TY - JOUR

T1 - Generation and characterization of recombinant human antibodies specific for native laminin epitopes

T2 - Potential application in cancer therapy

AU - Sanz, Laura

AU - Kristensen, Peter

AU - Russell, Stephen J

AU - Ramirez García, Jose

AU - Álvarez-Vallina, Luis

PY - 2001

Y1 - 2001

N2 - Laminins are specific cellular regulators that directly and indirectly control activities such as cell attachment and migration, differentiation and polarity, proliferation and apoptosis, and protease expression. Considering the centrality of these issues to tumor progression, the generation of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library of single chain antibodies was selected using intact mouse laminin, and five different clones were identified. All the antibodies were specific for their cognate antigen, as revealed by lack of cross-reactivity with other components of the basement membranes. A more extensive characterization of the panel indicated that these antibodies recognize the native protein through conformational epitopes. All of them reduced tumor cell attachment to laminin, suggesting that domains of the laminin molecule that are recognized by these antibodies likely bind to cell-surface receptors. The antibody fragments bind to mouse, rat and human laminin, and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications.

AB - Laminins are specific cellular regulators that directly and indirectly control activities such as cell attachment and migration, differentiation and polarity, proliferation and apoptosis, and protease expression. Considering the centrality of these issues to tumor progression, the generation of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library of single chain antibodies was selected using intact mouse laminin, and five different clones were identified. All the antibodies were specific for their cognate antigen, as revealed by lack of cross-reactivity with other components of the basement membranes. A more extensive characterization of the panel indicated that these antibodies recognize the native protein through conformational epitopes. All of them reduced tumor cell attachment to laminin, suggesting that domains of the laminin molecule that are recognized by these antibodies likely bind to cell-surface receptors. The antibody fragments bind to mouse, rat and human laminin, and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications.

KW - Cancer

KW - Extracellular matrix

KW - Human antibodies

KW - Laminin

KW - Phage display

UR - http://www.scopus.com/inward/record.url?scp=0035667982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035667982&partnerID=8YFLogxK

U2 - 10.1007/s00262-001-0235-5

DO - 10.1007/s00262-001-0235-5

M3 - Article

C2 - 11776378

AN - SCOPUS:0035667982

VL - 50

SP - 557

EP - 565

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 10

ER -