To facilitate tumor colonization by adoptively transferred cells of the imm
une system, we created a chimeric cell adhesion molecule that mediates tumo
r-specific homing by binding to the integrin alpha v beta 3 on angiogenic e
ndothelial cells, A high-affinity cell adhesion molecule for integrin alpha
v beta 3 was generated by fusing the disintegrin kistrin to the transmembr
ane adhesion molecule CD31/PECAM-1, This chimeric cell adhesion molecule, t
ermed KISS31, mediates adhesion of lymphoid cells to soluble recombinant in
tegrin alpha v beta 3 and to endotheliomal monolayers in vitro, KISS31-expr
essing lymphoid cells accumulate in angiogenic tumors in two in vivo models
, in B16/129 melanoma xenografts on the chick chorioallantois and in s.c. g
rowing 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 experi
mental mechanism that targets living cells to tumors by redirecting their h
oming pattern.