T cells expressing a HER2-specific chimeric antigen receptor as treatment for breast cancer

Abstract

Abstract HER2 is a member of the growth factor receptor family. It is very weakly expressed in the few epithelial cells in normal tissue. The HER2 gene and protein are overexpressed in many solid tumors. Thus, there are many advantages of targeting HER2 in tumor therapy. Tumor relapse can be prevented by chimeric antigen receptor (CAR) T-cell therapy. The efficacy of CAR-T-cell therapy against tumors can be improved by adding a hinge region to the CAR structure. Here, we constructed a second-generation CAR with a high-affinity scFv derived from a humanized anti-Her2 antibody and a CD8 hinge region. The CAR was transduced into T cells by lentiviral transfection. The modified CAR-T cells specifically targeted Her2 + tumor cells in vitro and in clinically relevant syngeneic and xenogeneic mouse models of Her2 + breast cancer. The modified CAR-T cells specifically recognized Her2 + breast cancer cells. The effect of the CAR-T cells against Her2 + breast cancer cells in vitro was in line with their efficacy in xenogeneic mouse models. Thus, these modified CAR-T cells may be a therapy for Her2 + breast cancer.