Single-chain antibody-based gene therapy: Inhibition of tumor growth by in situ production of phage-derived human antibody fragments blocking functionally active sites of cell-associated matrices

L. Sanz, P. Kristensen, B. Blanco, S. Facteau, Stephen J Russell, G. Winter, L. Álvarez-Vallina

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Experimental evidence suggests that blocking the interactions between endothelial cells and extracellular matrix (ECM) components may provide a potent and general strategy to inhibit tumor neovascularization. Based on these considerations, we have focused our efforts on laminin, component of the vascular basement membrane of every tumor-associated vessel, which serves an essential role in tube formation. We screened anti-laminin single-chain antibody fragments (scFv) derived from a human phage-display library and identified one that blocks the formation of capillary-like structures in vitro. This scFv inhibits angiogenesis in vivo in the chick embryo chorioallantoic membrane assay and prevents the establishment and growth of subcutaneous tumors in mice, either when administered as bolus protein therapy or when produced locally by gene-modified tumor cells. Our work represents the first demonstration of a direct in vivo therapeutic effect of a single-chain antibody secreted by gene-modified mammalian cells. These results open the way for a new antibody-based gene therapy strategy of cancer.

Original languageEnglish (US)
Pages (from-to)1049-1053
Number of pages5
JournalGene Therapy
Volume9
Issue number15
DOIs
StatePublished - 2002

Fingerprint

Single-Chain Antibodies
Immunoglobulin Fragments
Genetic Therapy
Bacteriophages
Catalytic Domain
Growth
Laminin
Neoplasms
Chorioallantoic Membrane
Therapeutic Uses
Chick Embryo
Basement Membrane
Genes
Libraries
Extracellular Matrix
Blood Vessels
Endothelial Cells
Antibodies
Proteins

Keywords

  • Cancer
  • Extracellular matrix
  • Gene therapy
  • Laminin
  • Single-chain antibody

ASJC Scopus subject areas

  • Genetics

Cite this

Single-chain antibody-based gene therapy : Inhibition of tumor growth by in situ production of phage-derived human antibody fragments blocking functionally active sites of cell-associated matrices. / Sanz, L.; Kristensen, P.; Blanco, B.; Facteau, S.; Russell, Stephen J; Winter, G.; Álvarez-Vallina, L.

In: Gene Therapy, Vol. 9, No. 15, 2002, p. 1049-1053.

Research output: Contribution to journalArticle

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