Eric T Ebert

Triple negative breast cancer (TNBC) is a highly aggressive form of breast cancer with limited treatment options. One of the potential treatments for TNBC is CCN5 (or WISP2) protein from the CCN family of matricellular proteins. In vitro studies revealed that CCN5 effectively reduces the proliferation and invasion of TNBC cells by binding to the a6b1 integrin. However, CCN5 has not been tested systematically in vivo for the treatment of TNBC. Because CCN5 has a small molecular weight (29 kDa), it will be subjected to fast renal clearance in the body. Thus, the residence time of CCN5 in the systemic circulation is reduced, potentially lowering its effectiveness as a therapeutic agent for TNBC. Therefore, the goals of this project are to (a) increase the size and/or hydrodynamic radius of CCN5 by conjugating it with various polyethylene glycols (PEG) to make CCN5-PEGs; (b) determine binding properties of  CCN5-PEGs to the a6b1 integrin receptor; (c) evaluate the in vitro activity of  CCN5-PEGs in TNBC; and (d) evaluate in vivo clearance of CCN5-PEGs. We hypothesize that CCN5-PEGs will have better physical stability and pharmacokinetic profiles than the parent CCN5, while maintaining its biological activity against TNBC. The hope is that CCN5-PEGs will have better therapeutic efficacy than the parent CCN5.