Novel anti-CD20 antibody TGLA with enhanced antibody-dependent cell-mediated cytotoxicity mediates potent anti-lymphoma activity

Abstract 

Rituximab is the first anti-cancer antibody approved by the FDA for the treatment of B-cell lymphoma. However, its efficacy remains variable and often modest. Some patients are initially unresponsive to rituximab or later develop resistance to it, and require alternative therapies. Rituximab activity has been thought to involve antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and apoptosis. Present studies suggest that the patients unresponsive to rituximab may be helped with other CD20 antibodies with enhanced activities. In this study, we characterized a novel anti-CD20 chimeric antibody, TGLA, which binds to various B-cell lines specially and shares an epitope with rituximab. TGLA shows equal activities with rituximab, such as CDC, cell growth arrest and so on. Interestingly, TGLA also shows significant ADCC activity. Immunotherapeutic studies further show that TGLA is far more effective in delaying tumor growth than rituximab. These findings suggest that the ADCC-enhanced anti-CD20 antibody TGLA might be an alternative therapeutic agent for B-cell lymphoma.

Abbreviations: ADCC, antibody-dependent cellular cytotoxicity, C2B8, rituximab, CDC, complement-dependent cytotoxicity, CHO, chinese hamster ovary, FCM, flow cytometry, FITC, fluorescein isothiocyanate, mAb, monoclonal antibody, PBMC, peripheral blood mononuclear cells, PBS, phosphate buffered saline, PVDF, polyvinylidene difluoride, TGLA-FITC, FITC-conjugated TGLA antibodies

Keywords: Anti-CD20 monoclonal antibody, TGLA, Rituximab, ADCC, Immunotherapy