Generation of gene-modified T cells reactive against the angiogenic kinase insert domain-containing receptor (KDR) found on tumor vasculature

Hum Gene Ther. 2000 Dec 10;11(18):2445-52. doi: 10.1089/10430340050207939.

Abstract

The destruction of newly forming tumor vasculature is a promising approach to inhibit tumor growth. The goal of the present study was to investigate whether human lymphocytes gene modified to express a chimeric receptor specific for the angiogenic endothelial cell receptor, KDR, could react against KDR(+) cells. Gene-modified lymphocytes specifically lysed KDR(+) cells and secreted cytokines in response to KDR(+) target cells including human umbilical vein endothelial cells (HUVECs). Anti-KDR lymphocytes induced HUVECs to secrete the chemokine interleukin 8 and upregulate the adhesion molecules VCAM and E-selectin, which may be important in the recruitment of further immune effector cells to tumor. These KDR-specific lymphocytes may be useful in the adoptive immunotherapy of a broad range of cancers by inducing immune-mediated destruction of tumor neovasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD28 Antigens / genetics
  • Cell Adhesion
  • Cell Line
  • Cells, Cultured
  • Cytokines / biosynthesis
  • E-Selectin / metabolism
  • Endothelium, Vascular / cytology
  • Flow Cytometry
  • Gene Transfer Techniques
  • Humans
  • Interleukin-8 / biosynthesis
  • Neoplasms / blood supply*
  • Neovascularization, Pathologic*
  • Protein Structure, Tertiary
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Fc / metabolism
  • Receptors, Growth Factor / genetics*
  • Receptors, Growth Factor / metabolism*
  • Receptors, Vascular Endothelial Growth Factor
  • T-Lymphocytes / metabolism*
  • Transduction, Genetic
  • Umbilical Veins / cytology
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • CD28 Antigens
  • Cytokines
  • E-Selectin
  • Interleukin-8
  • Receptors, Fc
  • Receptors, Growth Factor
  • Vascular Cell Adhesion Molecule-1
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor