Date of Award

6-2020

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2020.

Department

Bioengineering

First Advisor

Bill Lu

Abstract

Cancer is one of the leading causes of death in the United States1. This disease has impacted billions worldwide and has led to an ever-increasing burden on the healthcare system. Over the last couple of years, researchers have improved upon conventional cancer therapy that includes chemotherapy, radiation, and surgery. One novel approach is immunotherapy, which shows great potential because it has the ability to directly target cancerous cells2. This is a viable treatment because most cancers develop the ability to block immune pathways and evade the killer immune cells in what is known as cancer immune escape. One such pathway that is inhibited during the progression of specific cancers is the PD-L1 and PD-1 pathway thus inhibiting this pathway can be an effective treatment of advanced cancers3. To improve upon the efficacy of certain immunotherapies, we engineered a novel delivery method using exosomes to target this specific pathway. We focused on exosomes due to the nanovesicles ability to penetrate tissue better, the longer half-life of the treatment, and the biocompatibility of naturally derived vesicles. To complete this task, we focused on successfully integrating our exosomes expression vector in HEP-G2 and HK-2 cell lines. Next, we verified production of the engineered exosomes through the process of cotransfection using a known exosome-specific marker vector. Our results are valuable as they prove successful exosome plasmid vector integration. Furthermore, our study is a proof of concept that exosomes can be manipulated to express surface proteins; having the potential of interrupting immune evading pathways of numerous diseases.

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