A chimeric cell adhesion molecule mediates homing of lymphocytes to vascularized tumors.

Abstract

To facilitate tumor colonization by adoptively transferred cells of the immune system, we created a chimeric cell adhesion molecule that mediates tumor-specific homing by binding to the integrin alpha(v)beta3 on angiogenic endothelial cells. A high-affinity cell adhesion molecule for integrin alpha(v)beta3 was generated by fusing the disintegrin kistrin to the transmembrane adhesion molecule CD31/PECAM-1. This chimeric cell adhesion molecule, termed KISS31, mediates adhesion of lymphoid cells to soluble recombinant integrin alpha(v)beta3 and to endotheliomal monolayers in vitro. KISS31-expressing lymphoid cells accumulate in angiogenic tumors in two in vivo models, in B16/129 melanoma xenografts on the chick chorioallantois and in s.c. growing Lewis lung carcinoma in mice. Our data indicate that expression of KISS31 on lymphoid cells confers tumor-specific homing. This is, to our knowledge, the first example of an experimental mechanism that targets living cells to tumors by redirecting their homing pattern.