Leukemia Therapeutic Antibody Program
We are developing monoclonal antibody (mAbs) candidates discovered by our leukemia therapeutic antibody program. We are completing preclinical studies with a series of chimeric mAbs to select drug candidates for the treatment of chronic lymphocytic leukemia (CLL) and acute mylogenous leukemia (AML).
Nuvelo's mAb Development Process
Therapeutic mAbs represent the most exciting class of drugs to treat leukemia. Through its genomic discovery effort, we have identified three new mAb targets for leukemia. We have generated a series of high affinity and selective mAbs against cell surface receptors restricted to lymphoid and myeloid cells. These mAbs are potent in cytotoxic assays and murine cancer models.1
Our lead mAb was developed against the extra cellular domain of the CD2-related cell surface receptor, NTB-A. NTB-A is a novel cell surface receptor that is primarily expressed on lymphoid cells, including B lymphocytes from CLL and lymphoma patients. We have generated a NTB-A mouse-human chimeric antibody (IgG1) and conducted extensive ex vivo and preclinical studies. NTB-A mAb is a potent cytotoxic agent against B lymphocytes from CLL patients. Similar to Rituxan® (rituximab), NTB-A mAb acts as a potent anti-cancer agent in mouse xenograft models.1 In addition, while expression of Rituxan® CD20 target on B cells is down regulated in B cells from CLL patients, NTB-A expression is unchanged in cells from normal and CLL patients.
NTB-A mAbs Are Effective in Ex Vivo and Murine Tumor Models
In addition to NTB-A mAb, we identified two mAb targets that we are currently studying for the treatment of AML. We have developed mAbs (NU2444 and NU10458) against both targets, conducted ex vivo cytotoxic assays on blast cells from AML patients and generated a chimeric mAb, which are currently being assessed in murine tumor models.
Leukemia Therapeutics: mAbs Pipeline
1. Korver et al. The lymphoid cell surface receptor NTB-A: a novel monoclonal antibody target for leukaemia and lymphoma therapeutics. Br J Haematol 137 (2007). (http://www.blackwellsynergy.com/doi/abs/10.1111/j.1365-2141.2007.06569.x)