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    GCS Thesis

    Stephanie Zelenetz

    Project title: Recombinant Synthesis of Micelle-Forming Diblock Polypeptides For Cancer Immunotherapy

    GC Focus: Engineer Better Medicines

    Advisor: Ashutosh Chilkoti

    Abstract:

    Checkpoint blockades and adoptive T cell therapy have highlighted recent breakthroughs in cancer immunotherapy, but clinically effective cancer vaccines have yet to be achieved. By leveraging biomaterials for the delivery of antigen and adjuvant it is possible to fine-tune an anticancer immune response. Nanoparticles have demonstrated tremendous potential for the enhancement of immunotherapies by promoting increased antigen uptake, programming accumulation in the lymph nodes, and decreasing clearance. Here we describe the use of a diblock consisting of reslin-like polypetides (RLPs), hydrophobic repetitive proteins, and elastin-like polypeptides (ELPs), hydrophilic repetitive protein biopolymers for a cancer vaccine consisting of antigen and negatively charged adjuvants, such as CpG. RLP-ELP diblocks, a novel class of amphiphilic diblock polypeptides, are a strong choice for such as they provide a robust platform for creating micelles of a given size and morphology. Here, we created a library of Ova-RLP-ELP-K12 constructs and successfully expressed and purified Ova-RLP140-ELP180-K12 and Ova-RLP180– ELP1160-K12. We have shown the binding of Ova-RLP140-ELP180-K12 to CpG and the protein’s self-assembling behavior. Further characterization of different RLP-ELP variants will be used to determine the fusion that is the ideal candidate for a nanoparticle-based vaccine platform.

    GCS Poster

    GCS Thesis

    Reflection and Future Plans:

    My GCS experience has allowed me to explore the intersection of engineering and medicine by developing a biomaterial-based cancer vaccine.This comprehensive research experience allowed me to gain invaluable skills, from protein engineering to vaccine development, that will one day allow me to achieve my goal of developing a therapeutic that can be  translated into the clinic. My involvement in the GCS program has supplemented my research experience by providing me with exposure to the other factors that dictate a medicine’s success. For instance, my global experience allowed me to travel to Europe and learn about how differences in healthcare systems can impact cancer treatment, and which drugs are on the market. Additionally, my I&E component allowed me to gain insight into the entrepreneurship aspect of drug development, and to consider the viability of a drug on the market from an economic standpoint. Overall, the GCS program has entailed me to get a more complete picture of engineering better medicines: from the need to the science to the practical factors that govern a therapy’s success.

    After graduation I will be continuing my education by pursuing a PhD at Northwestern University in the Fall of 2020. I hope to conduct research to develop another biomaterial-based immunotherapy. One day I hope to work in industry to engineer a novel therapeutic that can be translated into the clinic.