A chimeric cell adhesion molecule mediates homing of lymphocytes to vascularized tumors.
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.
Wiedle
G
G
Department of Pathology, Centre Médical Universitaire, Geneva, Switzerland.
Johnson-Léger
C
C
Imhof
B A
BA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D002645:Chickens; D016219:Immunotherapy, Adoptive; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000628:therapy*; D010455:Peptides / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology*; D014407:Tumor Cells, Cultured
D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins; C067623:kistrin