BME PhD Thesis Proposal Presentation

Date: Monday, April 17th

Time: 1:00pm

Location: EBB CHOA seminar room, Georgia Tech

Advisor: 

Dr.Krishnendu Roy 

Committee: 

Dr. M.G.Finn (Chemistry and Biochemistry)

Dr.Robert Guldberg

Dr.Ravi Kane

Dr.Susan Thomas

Title: Design and Development of Synthetic Nanoparticle Antibodies to Deplete Selected Target Cells for Cancer Immunotherapy

Abstract: 

Monoclonal antibody(mAb) treatment for cancer has been developed for over three decades and has proved its efficacy in a number of hematological malignancies and solid tumors. A handful of available mAbs (e.g.,atezolizumab) take advantage of antibody-dependent immune responses to eliminate the suppressive cells/proteins and restore anti-cancer immunity. Some other mAbs (e.g.,Trastuzumab, Rituximab), which are able to bind to cancer-associated antigens(e.g. Her2), can kill tumor targets by eliciting antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/ADCP). However, the application of monoclonal antibodies as therapeutics is greatly limited by their complicated production procedure, high production cost as well as limited deep tissue penetration. Additionally, many important immunological targets, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells, still lack direct mAb treatments. A few types of artificial antibodies, including nanobody, minibody and peptibody, which are developed by alternation of the orignal mAb structures, achieved higher tumor-to-blood distribution ratio, but still suffer from other drawbacks associated with their production and application similar to those of mAbs. We propose to develop synthetic nanoparticle antibodies (SNAbs) , which are Janus nanoparticles multi-valently displaying both binding ligands for the selected targets and Fc-mimicking ligands that can activate Fc receptors on the immune effector cells. Our primary hypothesis is that the designed SJNAs could induce ADCC/ADCP of cellular targets efficiently both in vitro and in vivo. Investigation will be conducted on two types of SNAbs: one for MDSCs and one for Her2-expressing cancer cells. We will perform both in vitro study on Fc-receptor-mediated signaling triggered by the SNAbs as well as in vivo assessment of their therapeutic potential in murine tumor models. We believe that SNAbs can not only be a functional alternative to conventional mAbs for target cell depletion in cancer, but also possess potential advantages including simpler fabrication procedure, flexible platform and better tumor penetration.