NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from Chronic Lymphocytic Leukemia (CLL) and lymphoma patients. We have generated a series of murine and chimeric mAbs against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional Complement Dependent Cytotoxicity (CDC) and Antibody Dependent Cellular Cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and NK cells, CDC and ADCC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by siRNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti-NTB-A mAbs demonstrated anti-tumor activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in SCID mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukemia and lymphomas.

Topics:
leukemia, lymphoid cells, lymphoma, monoclonal antibodies, antibodies, chronic b-cell leukemias, chronic lymphocytic leukemia, cytotoxicity, immunotherapy, membrane proteins

Author notes

Disclosure:Employment: Three authors are employed by Nuvelo, Inc. Ownership Interests:; Three authors own stock options in Nuvelo, Inc. Honoraria Information: Work at the Cleveland Clinic described in this abstract is sponsored by Nuvelo, Inc.

2007, The American Society of Hematology
2007
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