RETRACTED: Targeted immunotherapy for HER2-low breast cancer with 17p loss
Yujing Li, Yifan Sun, Michael Kulke, Torsten Hechler, Kevin Van der Jeught, Tianhan Dong, Bin He, Kathy D. Miller, Milan Radovich, Bryan P. Schneider, Andreas Pahl, Xinna Zhang, Xiongbin Lu
Abstract
, a gene encoding the catalytic subunit of RNA polymerase II that is essential for cell survival. Therefore, breast cancer cells with heterozygous loss of 17p are extremely sensitive to the inhibition of POLR2A via a specific small-molecule inhibitor, α-amanitin. Here, we demonstrate that α-amanitin-conjugated trastuzumab (T-Ama) potentiated the HER2-targeted therapy and exhibited superior efficacy in treating HER2-low breast cancer with 17p loss. Moreover, treatment with T-Ama induced immunogenic cell death in breast cancer cells and, thereby, delivered greater efficacy in combination with immune checkpoint blockade therapy in preclinical HER2-low breast cancer models. Collectively, 17p loss not only drives breast tumorigenesis but also confers therapeutic vulnerabilities that may be used to develop targeted precision immunotherapy.