Cytotoxicity of a novel anti-ICAM-1 immunotoxin on human myeloma cell lines.
We have generated a murine monoclonal antibody (UV3) which recognizes an epitope on ICAM-1 expressed on myeloma cells. By flow cytometric analysis, the epitope on ICAM-1 recognized by this antibody is strongly expressed on human myeloma cells, pre-B leukemia cells and Burkitt's lymphoma cell lines. Most human T cell lines are weakly positive. The antibody does not react with red blood cells, polymorphonuclear leukocytes (PMNs) or resting B lymphocytes from normal donors, and reacts very weakly with resting T cells. Immunohistochemical assays indicate that the antibody does not react with normal liver, kidney, heart, brain, thymus or lung. An immunotoxin (IT) was prepared by coupling UV3 to deglycosylated ricin A-chain (dgA). In protein synthesis inhibition assays it was highly cytotoxic to the human myeloma cell lines HS-SULTAN (IC50 = 1 x 10(-11)M) and ARH-77 (IC50 = 9 x 10(-11)M), but not to cell lines of T cell lineage or most cell lines of the B lineage. Our results suggest that the UV3-dgA may have therapeutic potential for the treatment of human multiple myeloma.
Huang
Y W
YW
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Burrows
F J
FJ
Vitetta
E S
ES
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D000922:Immunotoxins / Q000276:immunology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000922:Immunotoxins; D018799:Intercellular Adhesion Molecule-1