Characterization of a Novel Bispecific Antibody That Activates T Cells In Vitro and Slows Tumor Growth In Vivo.

Characterization of a Novel Bispecific Antibody That Activates T Cells In Vitro and Slows Tumor Growth In Vivo. Monoclon Antib Immunodiagn Immunother. 2019 Dec;38(6):242-254 Authors: Chornoguz O, Leettola CN, Leander K, Brosnan K, Emmell E, Chiu ML, Santulli-Marotto S Abstract Although CD3 T cell redirecting antibodies have been successfully utilized for the treatment of hematological malignancies (blinatumomab), the T cell signaling pathways induced by these molecules are incompletely understood. To gain insight into the mechanism of action for T cell redirection antibodies, we created a novel murine CD3xEpCAM bispecific antibody that incorporates a silent Fc to dissect function and signaling of murine CD8 OT1 T cells upon stimulation. T cell-mediated cytotoxicity, cytokine secretion, expression of activation markers, and proliferation were directly induced in T cells treated with the novel CD3xEpCAM bispecific molecule in vitro in the presence of epithelial cell adhesion molecule (EpCAM) expressing tumor cells. Nanostring analysis showed that CD3xEpCAM induced a gene expression profile that resembled antigen-mediated activation, although the magnitude was lower than that of the antigen-induced response. In addition, this CD3xEpCAM bispecific antibody exhibited in vivo efficacy. This is the first study that investigates both in vitro and in vivo murine CD8 T cell function and signaling induced by a CD3xEpCAM antibody having a silent...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research