Use of a cocktail of monoclonal antibodies and human complement in selective killing of acute lymphocytic leukemia cells

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Abstract
Autologous remission bone marrow is a potential source of repopulative stem cells after ablative chemoradiotherapy of tumor patients. Even with remission bone marrow, one major obstacle to use of autologous bone‐marrow support is the danger of reinfusing viable tumor cells. This report describes a purging protocol with human complement, which seems suitable for eliminating acute lymphatic leukemia (ALL) cells of the common ALL type. Lysis of ALL blasts is induced with a cocktail of 3 monoclonal antibodies of IgM type (termed VIB‐pool). These are directed against the CALLA (CD 10) antigen (VIL‐AI antibody) and against 2 different epitopes of the CD24 surface structure (VIB‐C5 and VIB‐E3 antibodies). The purging efficiency was evaluated with leukemic cell lines of the common ALL type (Reh‐6 and Nalm‐6) and with blast cells from common ALL patients. Optimal lysis was obtained with antibody and human serum concentrations as low as I μg/ml and 7% respectively. As a standard purging protocol we propose one 20‐min incubation at room temperature with antibody followed by two 30‐min incubations at 37°C with 25% human complement. In dye exclusion tests 99% purging efficiency and in clonogenic assays detecting elimination of up to 5 logs of clonogenic tumor cells 99.99% (= 4 logs) purging efficiency were achieved. Treatment with VIB‐pool and human complement had no negative effect on the growth of the normal hemopoietic progenitor cells CFU‐GM, CFU‐E and BFU‐E.