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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • November 2011

Published In

Volume / Issue

  • 155 / 4

Start / End Page

  • 426 - 437

PubMed ID

  • 21902688

Pubmed Central ID

  • 21902688

Electronic International Standard Serial Number (EISSN)

  • 1365-2141

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2141.2011.08857.x

Language

  • eng

Conference Location

  • England