Monoclonal antibodies to lymphocyte function-associated antigen-1 inhibit invasion of human lymphoma and metastasis of murine lymphoma.
The leukocyte integrins are cell adhesion molecules which play pivotal roles in the development of a variety of immune responses including T-cell-mediated cytotoxicity, lymphocyte proliferation, macrophage presentation of antigen, and adhesion of leukocytes to vascular endothelium. The relevance of lymphocyte function-associated antigen-1 (LFA-1) to leukocyte malignancies is currently under examination in a number of laboratories. Here, we present evidence demonstrating that LFA-1 plays a role during the in vitro invasion of human endothelium by JY lymphoma cells and during in vivo metastasis of two distinct models of murine leukemia: P815 mastocytoma and EL4 lymphoma. When assayed in vitro, a murine anti-human LFA-1 (alpha subunit) monoclonal antibody (mAb) inhibits up to 80% of JY lymphoma cell invasion. When assayed in vivo, a rat anti-LFA-1 (alpha subunit) mAb significantly inhibited the development of experimental metastases, when administered concomitantly with either P815 or EL4 tumor cells. The leukocyte integrins, particularly LFA-1, may represent useful targets for the therapeutic modulation of metastasis.
Harning
R
R
Roberts Pharmaceutical Corporation, Research and Development Eatontown, NJ 07724.
Myers
C
C
Merluzzi
V J
VJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008113:Liver Neoplasms / Q000556:secondary; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D008223:Lymphoma / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009361:Neoplasm Invasiveness; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1