BME PhD Thesis Defense Presentation

Date: June 6th, 2019

Time: 11am-1pm 

Location: EBB, CHOA room

(Bluejeans call-in available at bottom)

Advisor: 

Dr.Krishnendu Roy 

Committee: 

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

Dr.Robert Guldberg (University of Oregon)

Dr.Ravi Kane

Dr.Susan Thomas

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

Abstract: 

Monoclonal antibodies (mAbs) have shown great promise as immunotherapy of cancer in the past decades. They mediate the antibody-dependent immune responses to eliminate the malignant or suppressive cells and proteins and restore anti-cancer immunity. However, the application of monoclonal antibodies as therapeutics is greatly hampered by its high production cost as well as high dosage required to generate significant therapeutic effect due to limited tissue penetration. Besides, monoclonal antibodies targeting some important immunological targets, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells, are still awaiting to be developed. 

Here, we have developed a novel type of artificial antibodies, the synthetic nanoparticle antibodies (SNAbs), which are Janus nanoparticles multivalently displaying both binding ligands for the selected cellular targets and Fc-mimicking ligands that can activate Fc receptors. Our primary hypothesis is that the designed SNAbs could induce ADCC/ADCP of cellular targets efficiently both in vitro and in vivo. A simple chemistry method to fabricate Janus gold nanoparticles and to modify these nanoparticles with peptide ligands was designed to make SNAbs. Myeloid derived suppressor cells are selected as our primary cell of interest. We evaluated the capability of SNAbs to target MDSCs in both ex vivo assays and in vivo tumor model systems. We showed that SNAbs can selectively induce antibody-dependent killing of MDSCs in the mixture of various types of immune cells and are also able to deplete MDSCs in a tumor model. The research completed in this thesis demonstrated that the SNAbs are a functional alternative to monoclonal antibodies and hold great promise as a potent immunotherapy for cancer. 

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