Activating Immunogenicity on Tumor Associated Antigens with Proximity Accelerated Reactions

Chemotherapy is regarded as one of the most common cancer treatments but fails in almost 90% of cases due to acquired resistance against anti-cancer drugs (1). The development of Multi-Drug Resistance (MDR) is a common limitation in all cancer treatment modalities however (1). Immunotherapy is a promising pathway in MDR cancer treatment for its ability to boost the body’s own immune system to attack and destroy cancer cells. Proximity-accelerated chemistry is a strategy used to speed up chemical reactions when the reactants are held in close proximity. This technique has been modified to produce the Ligand-Directed Nitrophenol Carbonate (LDNPC) chemistry seen in Figure 1 (2). In this method, a chosen ligand is conjugated to a nitrophenol carbonate and self-immolative linker which is attached to the drug payload (2). As the ligand binds to the target, nucleophilic residues peripheral to the binding site attack the molecule (affinity labelling). The linker is subsequently hydrolyzed releasing the drug payload. 

We hypothesize the synthesis of a LDNPC compound specific to the TNC receptor linked to the immunostimulant, imiquimod. 

Research presented in this poster is supported by National Cancer Institute of the National Institute of Health under award number 1R01CA234115 to Dr. Rock Mancini. The opinions and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the NIH or U.S. government.  

Communication: Through this research, I have been able to learn and practice my communication skills. In any form of research, communication is a necessity in order to have effectice procedings in the lab, but especially when working under a graduate student and with other undergraduates, it's been vital for me to learn these skills. I have been able to effectively communicate questions, directions, results, and next steps, all of which contribute to effective research and results. 

Teamwork: As I mentioned earlier, working in such a large lab has taught me how to work around and with others in a team to efficiently and effectively get my job done. I have also learned that working in a chemistry lab creates a lot of mess and waste, and that cleanup is not just a solo job, but something that everyone can participate in to help out and maintain the upkeep of the lab. Teamwork also involves collaboration and working with others to achieve a goal, which is something I have been witness to and participated in within the Mancini Lab. 

Critical Thinking: Organic synthesis involves a great deal of critical thinking. With each experiment, even the same conditions could result in a different product or mixture of products. Working in this lab has taught me how to look at the reaction and what is occuring and try to figure out where it could've gone wrong or what could've affected the results. Chemistry is never perfect or clean, so this has bee a big challenge over the past few years for me, but it has also taught me so much about critical thinking.