Abstract B36: Human serum albumin and affibody fusion proteins for targeted drug delivery to HER2 positive cells

Abstract

Abstract Human Epidermal growth factor Receptor 2 (HER2) has been reported to be over-expressed in 20-30% of the breast cancer patients and related to poor prognosis. Affibody ZHER2 is a small protein which has high affinity to HER2 screened by phage display. Human Serum Albumin (HSA), as the main protein in plasma, has been commonly used to extend the small peptides serum half-life. Its high solubility, stability and excellent ability to carry multiple ligands in blood stream make it a good candidate for drug delivery. In this presentation, we report the development of albumin-affibody fusion proteins in the aim of targeted delivering chemotherapeutics to HER2 positive cells. Two HSA fusion proteins have been successfully constructed, expressed and purified, one with a single ZHER2 domain at the albumin C terminus (rHSA-ZHER2) and the other has two tandem copies of ZHER2 (rHSA-(ZHER2)2). Both of the fusion proteins maintained the HER2 and fatty acid (FA) binding ability inherited respectively from the two parental proteins demonstrated by in vitro assays. Upon binding to the HER2, rHSA-ZHER2 only showed mild effect on HER2 positive SK-BR-3 cells, while rHSA-(ZHER2)2 significantly inhibited the proliferation of SK-BR-3 cells. More interestingly, a strong activation of both MAPK and AKT signaling was observed. Our results prove the feasibility of the fusion proteins to be used as drug carriers. Currently two formulations are under investigation, one is to complex the fusion protein with FA modified chemo drugs, and the other is to make them into nanoparticles. These two proteins not only can be explored as a potential drug delivery vehicle, but also may provide us with a good molecular tool to study the HER2 signaling pathway. Citation Format: Daoyuan Dong, Zhijun Li, Zhiyu Li. Human serum albumin and affibody fusion proteins for targeted drug delivery to HER2 positive cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B36.