Breast cancer and HER3; the possibilities of imaging with VHH probes

Abstract

Breast cancer is one of the most common cancers in the world and HER2-amplified breast cancer represents about a quarter of all breast cancer cases. HER2-amplified breast cancer is an aggressive form of breast cancer. In order to be able to diagnose this type of cancer in an early stadium and to find a specific treatment, research has been done on possible targets. Studies have pointed out that HER3 plays an important role in HER2-amplifed breast cancer and in breast cancer cases where endocrine resistance originated and that this might be a target for imaging and possible treatment. The use of Variable heavy chain of heavy-chain-only antibody (VHH) in optical imaging can simplify and improve the quality of imaging and treating breast cancer tumors. The images can be obtained faster and they might have better signal-to-background ratios than ones made with conventional antibodies, due to their particular features (such as seize, stability, and specificity). In this research we have investigated a number of VHHs that in the near future could be useful for HER3 imaging in breast cancer tumors. The VHHs tested did not activate the downstream pathway of HER3 and did not seem to compete with its ligand, neuregulin (except for E11 VHH). E11 showed binding to HER3 on the cell surface (being conjugated to a fluorophore) as well as with only the extracellular domain of HER3. Although the wanted high affinity was not found in this study, imaging with near infrared and ELISA showed that E11 had the best results from the tested VHHs. These results implicate that E11 posses some of the properties wanted for a probe for imaging, but that the affinity appears to be the limiting factor for the imaging of HER3 in breast cancer. Future research might point out a VHH that is able to bind with the wanted high affinity.