Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2⁺ Breast Cancer Metastasis to the Brain.

ABSTRACT: Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease.Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring

SUBMITTER: Priceman SJ 

PROVIDER: S-EPMC7685198 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature