anti-HER2 ATAC

`anti-HER2 ATAC` (also known as `trastuzumab-ATAC` or `HER2-ATAC`) is a preclinical antibody-drug conjugate (ADC) developed by Heidelberg Pharma Research. It belongs to a novel class of ADCs called Antibody Targeted Amanitin Conjugates (ATACs). The conjugate consists of the anti-HER2 monoclonal antibody trastuzumab (or a cysteine-engineered THIOMAB variant) site-specifically conjugated to the highly potent payload amanitin (specifically alpha-amanitin or an amanitin derivative) with a drug-to-antibody ratio (DAR) of approximately 2.0. Amanitin acts by binding to and inhibiting eukaryotic RNA polymerase II, thereby blocking cellular transcription and inducing apoptosis. This mechanism is independent of cell division, allowing the drug to target both proliferating and dormant tumor cells. Preclinical studies have demonstrated that anti-HER2 ATAC is highly effective in HER2-low breast cancer, particularly triple-negative breast cancer (TNBC) harboring a hemizygous loss of POLR2A/chromosome 17p deletion, which makes these cells highly sensitive to RNA polymerase II inhibition. It also induces immunogenic cell death (ICD) and shows synergistic anti-tumor efficacy when combined with immune checkpoint inhibitors.

Other names

amanitin-HER2 antibody drug conjugateamanitin-HER-2 antibody drug conjugateamanitin-HER 2 antibody drug conjugateanti-HER2-THIOMAB-ATACanti-HER-2-THIOMAB-ATACanti-HER 2-THIOMAB-ATACHER2-ATACHER-2-ATACHER 2-ATACtrastuzumab-ATACtrastuzumab-amanitin