IGM MONOCLONAL-ANTIBODY JD118 RECOGNIZES AN INDUCIBLE ANTIGEN TARGET FOR HUMAN-COMPLEMENT-MEDIATED CYTOTOXICITY AGAINST NEOPLASTIC B-CELLS

Cancer therapy using unconjugated monoclonal antibodies (mAb) has been limited by the lack of immune effector function of the mAb and antige nic modulation. JD118 is a cytotoxic murine IgM mAb with reactivity re stricted to a subset of normal B cells, some monocytic series cells, a nd a large percentage of B cell hematopoietic neoplasms including acut e and chronic leukemias and lymphomas. Specificity was determined on s everal hundred normal and neoplastic, hematopoietic and non-hematopoie tic cells and tissues, as well as progenitor cells. JD 1 18 was able t o kill fresh human leukemias and lymphomas in the presence of human se rum as a complement source with an LD50 Of 100 ng/ml. At this mAb conc entration, fewer than 4% of more than 10(5) available target sites wer e bound. Killing was not affected by changes in antigen expression obs erved during the cell cycle nor by loss of cell-surface targets via an tigenic modulation. Cytotoxicity could be achieved with human serum di luted as low as 5%, suggesting that complement depletion in vivo shoul d not limit activity. Autologous human serum could be used effectively as a complement source. The JD118 antigen target has not been identif ied, but it appears to be a glycoprotein. Up-regulation of antigen exp ression on normal B cells and chronic lymphocytic leukemia cells in vi tro resulted in antigen-negative neoplasms becoming positive and thus targets for JD118 killing. The restricted expression, potent cytotoxic characteristics, and potential for up-regulation of its antigen make JD118 a possible candidate for ex vivo autologous bone marrow purging and in vivo therapeutic trials in patients with B cell neoplasms.