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Development of a new fully human anti-CD20 monoclonal antibody for the treatment of B-cell malignancies.

Bornstein, Gadi Gazit; Quéva, Christophe; Tabrizi, Mohammad; van Abbema, Anne; Chavez, Carlos; Wang, Ping; Foord, Orit; Ahluwalia, Kiran; Laing, Naomi; Raja, Sandhya; Wen, Shenghua; Green, Larry L; Yang, Xiaodong; Webster, Carl; Stewart, Ross; Blakey, David.
Invest New Drugs; 28(5): 561-74, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19626278
Despite the widespread use of rituximab, a chimeric monoclonal antibody with demonstrated efficacy in the treatment of non-Hodgkin's lymphomas, there is a recognized need to develop new agents with improved efficacy. Towards this end, using XenoMouse technology, a fully human IgG1 anti-CD20 monoclonal antibody was generated. This antibody, denoted mAb 1.5.3, evoked enhanced pro-apoptotic activity in vitro, as compared to rituximab, in the Ramos lymphoma cell line. Also, mAb 1.5.3 mediated both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) similar to rituximab in human B-lymphoma lines. Interestingly, mAb 1.5.3 demonstrated superior ADCC compared to rituiximab when FcgammaRIIIa F/F allotype donors were profiled and superior cytolytic activity across multiple human B-lymphoma and chronic B-cell leukemia lines in an in vitro whole blood assay. Furthermore, mAb 1.5.3 exhibited enhanced anti-tumor activity in Ramos, Daudi, and Namalwa tumour xenograft models. Lastly, mAb 1.5.3 produced a superior B-cell depletion profile in lymph node organs and bone marrow as compared to rituximab in a primate pharmacodynamic (PD) model. These findings underscore the potential of mAb 1.5.3 to exhibit improved clinical activity in the treatment of B-cell malignancies compared to rituximab.
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