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.