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

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