Targeted Alpha Therapy Symposium

Targeted alpha therapy with anti-HER2 thorium-227 antibody-chelator conjugates (HER2-TTCs) in mouse xenograft models with varying levels of HER2 expression and resistance to current state-of-the-art therapies

Not scheduled

15m

Fairmont Château Laurier Hotel

Speaker

Dr Jenny Karlsson (Bayer AS)

Description

Targeted thorium conjugates (TTCs) represent a new class of therapeutic radiopharmaceuticals for the targeted alpha therapy (TAT) of cancer. The human epidermal growth factor receptor 2 (HER2) is overexpressed in several cancers and is a validated target for the treatment of breast and gastric cancer, also serving as a prognostic and predictive biomarker. During treatment, many patients become resistant or are not eligible for these therapies, due to low expression levels of the target (~55%). Therefore there exists a high unmet medical need for new drugs with alternative mechanisms of action targeting HER2. We describe an antibody conjugate capable of delivering thorium-227 (227Th) to cancer cells expressing the human epidermal growth factor receptor 2 (HER2). The preclinical pharmacological in vivo characterization of the HER2-TTC, with a focus on trastu¬zumab and T-DM1 (trastuzumab-DM1)-resistant and HER2 low expressing mouse xenograft models, are presented.