Background: Human monoclonal antibody (mAb) 216 is a naturally occurring IgM cytotoxic mAb that binds to a glycosylated epitope on the surface of B-lymphocytes. This study investigated if this mAb could bind and kill acute lymphoblastic leukemia (ALL) B-progenitor lymphoblasts in vitro. ALL cell lines were used to determine if combining mAb 216 with chemotherapeutic drugs would enhance killing and cell lines were used to measure cytotoxicity by mAb 216 with human complement.
Procedure: Expression of cell surface markers and mAb 216 epitope on fresh and banked ALL bone marrow samples was determined by flow cytometry. Fresh lymphoblasts were incubated for 20 hr with mAb 216 without complement to measure cytotoxicity. Cytotoxicity of ALL cell lines incubated with mAb 216 and vincristine (VCR) or human complement was determined using flow cytometry.
Results: Pre-B-ALL cells but not T-ALL cells are bound and killed by mAb 216. The combination of mAb 216 and VCR at sub-therapeutic levels demonstrated enhanced cytotoxicity beyond that observed for either agent alone. Incubation of mAb 216 with human complement increased cytotoxicity of ALL cell lines.
Conclusion: This increased cytotoxicity with chemotherapy and the functional ability of mAb 216 to use multiple pathways to induce cell death identify mAb 216 as a potentially novel therapeutic tool in the treatment of B-progenitor ALL. Based on the results from this preclinical study, a Phase I clinical trial with mAb 216 for the treatment of patients with relapsed or refractory B-lineage ALL is ongoing.
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