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

Cancer Res. 1999 Oct 15;59(20):5255-63.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Movement
  • Chickens
  • Immunotherapy, Adoptive*
  • Lymphocytes / immunology*
  • Lymphocytes / physiology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neoplasms, Experimental / therapy*
  • Peptides / physiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / physiology*
  • Receptors, Vitronectin / physiology
  • Recombinant Fusion Proteins / physiology*
  • Tumor Cells, Cultured

Substances

  • Peptides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Vitronectin
  • Recombinant Fusion Proteins
  • kistrin