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

M. H. Kershaw, J. A. Westwood, Z. Zhu, L. Witte, S. K. Libutti, P. Hwu

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2445-2452
Number of pages8
JournalHuman Gene Therapy
Volume11
Issue number18
DOIs
Publication statusPublished - Dec 10 2000

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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