A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo.

Human cluster of differentiation (CD) antigen 19 is a B cell-specific surface antigen and an attractive target for therapeutic monoclonal antibody (mAb) approaches to treat malignancies of B cell origin. MEDI-551 is an affinity-optimized and afucosylated CD19 mAb with enhanced antibody-dependent cellular cytotoxicity (ADCC). The results from in vitro ADCC assays with Natural Killer cells as effector cells, demonstrate that MEDI-551 is effective at lower mAb doses than rituximab with multiple cell lines as well as primary chronic lymphocytic leukaemia and acute lymphoblastic leukaemia samples. Targeting CD19 with MEDI-551 was also effective in several severe combined immunodeficiency lymphoma models. Furthermore, the combination of MEDI-551 with rituximab resulted in prolonged suppression of tumour growth, demonstrating that therapeutic mAbs with overlapping effector function can be combined for greater tumour growth inhibition. Together, the data demonstrate that MEDI-551 has potent antitumour activity in preclinical models of B cell malignancies. The results also suggest that the combination of the ADCC-enhanced CD19 mAb with an anti-CD20 mAb could be a novel approach for the treatment of B cell lymphomas.

Ward E ，Mittereder N ，Kuta E ，Sims GP ，Bowen MA ，Dall'Acqua W ，Tedder T ，Kiener P ，Coyle AJ ，Wu H ，Jallal B ，Herbst R ... -  《-》

B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody.

Herbst R ，Wang Y ，Gallagher S ，Mittereder N ，Kuta E ，Damschroder M ，Woods R ，Rowe DC ，Cheng L ，Cook K ，Evans K ，Sims GP ，Pfarr DS ，Bowen MA ，Dall'Acqua W ，Shlomchik M ，Tedder TF ，Kiener P ，Jallal B ，Wu H ，Coyle AJ ... -  《-》

Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia.

Horton HM ，Bernett MJ ，Pong E ，Peipp M ，Karki S ，Chu SY ，Richards JO ，Vostiar I ，Joyce PF ，Repp R ，Desjarlais JR ，Zhukovsky EA ... -  《-》

Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.

Lopes de Menezes DE ，Denis-Mize K ，Tang Y ，Ye H ，Kunich JC ，Garrett EN ，Peng J ，Cousens LS ，Gelb AB ，Heise C ，Wilson SE ，Jallal B ，Aukerman SL ... -  《JOURNAL OF IMMUNOTHERAPY》

The anti-CD20 antibody rituximab augments the immunospecific therapeutic effectiveness of an anti-CD19 immunotoxin directed against human B-cell lymphoma.

Flavell DJ ，Warnes SL ，Bryson CJ ，Field SA ，Noss AL ，Packham G ，Flavell SU ... -  《BRITISH JOURNAL OF HAEMATOLOGY》