Effects of human monoclonal antibody 216 on B-progenitor acute lymphoblastic leukemia in vitro.
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.


METHODS
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.


CONCLUSIONS
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.
Bieber
Marcia M
MM
Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, California, USA. bieber@stanford.edu
Twist
Clare J
CJ
Bhat
Neelima M
NM
Teng
Nelson N H
NN
D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000276:immunology; D002648:Child; D003165:Complement System Proteins / Q000276:immunology; D004354:Drug Screening Assays, Antitumor; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology* / Q000628:therapy; D013048:Specimen Handling; D014021:Tissue Preservation
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003165:Complement System Proteins