Beschreibung:
Abstract GBR 401 is a humanized monoclonal antibody directed against domain 2 of human B-lymphocyte antigen CD19 and displays a number of mechanisms which can specifically target and kill B cells. Glenmark is developing this product as a B-cell depleting agent for B cell malignancies. CD19 is the archetypal B cell marker and is used in the diagnosis of B cell lymphomas/ leukemias by the identification of abnormal B cell numbers and/or populations. Expression of CD19 is found in the majority of B cell lineage malignancies including, but not limited to non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia. Given its role as a signaling molecule, an antibody directed against CD19 might be predicted to affect the progression of lymphomas and leukemias. GBR 401 is a humanized IgG1 which can specifically kill CD19 bearing cells with very efficient in vitro antibody-dependent cellular cytotoxicity (ADCC) and rapid-onset apoptosis-inducing abilities. It also can inhibit the proliferation of CD19+ tumor cells but has little to no complement dependent cytotoxicity (CDC), at least, in vitro. The in vivo anti-B cell activity of GBR 401 was evaluated using human peripheral blood mononuclear cell (huPBMC) graft models in SCID mice. GBR 401 significantly depleted human B cells in grafted mice at levels down to 0.1mg/kg compared to an isotype control. GBR 401 also produced approximately 50% depletion or EC50 at 0.02mg/kg. These in vitro and in vivo pharmacology data provide a rationale for the clinical testing of GBR 401 in patients with CD19+hematologic malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C164.