학술논문
Antitumor Efficacy of a Bispecific Antibody That Targets HER2 and Activates T Cells.
Document Type
Article
Author
Junttila, Teemu T.; Ji Li; Johnston, Jennifer; Hristopoulos, Maria; Clark, Robyn; Ellerman, Diego; Bu-Er Wang; Yijin Li; Mathieu, Mary; Guangmin Li; Young, Judy; Luis, Elizabeth; Phillips, Gail Lewis; Stefanich, Eric; Spiess, Christoph; Polson, Andrew; Irving, Bryan; Scheer, Justin M.; Junttila, Melissa R.; Dennis, Mark S.
Source
Subject
*CANCER immunotherapy
*T cells
*CANCER cells
*CANCER treatment
*TUMOR growth
*
*
*
*
Language
ISSN
0008-5472
Abstract
Clinical results from the latest strategies for T-cell activation in cancer have fired interest in combination immunotherapies that can fully engage T-cell immunity. In this study, we describe a trastuzumab-based bispecific antibody, HER2-TDB, which targets HER2 and conditionally activates T cells. HER2-TDB specifically killed HER2-expressing cancer cells at low picomolar concentrations. Because of its unique mechanism of action, which is independent of HER2 signaling or chemotherapeutic sensitivity, HER2-TDB eliminated cells refractory to currently approved HER2 therapies. HER2-TDB exhibited potent antitumor activity in four preclinical model systems, including MMTV-huHER2 and huCD3 transgenic mice. PD-L1 expression in tumors limited HER2-TDB activity, but this resistance could be reversed by anti-PD-L1 treatment. Thus, combining HER2-TDB with anti-PD-L1 yielded a combination immunotherapy that enhanced tumor growth inhibition, increasing the rates and durability of therapeutic response. [ABSTRACT FROM AUTHOR]