Amanda Billups


Synthetic Oncolytic Polymer Induces Immunogenic Cell Death

Immunogenic cell death (ICD) is of interest for cancer treatment due to its ability to initiate an anti-tumor immune response which can mediate anticancer immunity. Oncolytic peptides and polymers are an emerging strategy to evoke ICD which may address limitations like the induction of apoptotic cell death which can promote tumor growth found with conventional cancer therapies such as chemotherapy, immunotherapy, and focal ablation. A synthetic oncolytic polymer poly(6-aminohexyl methacrylate) (PAHM) was studied to determine if it induces ICD in adult pancreatic adenocarcinoma (AsPC-1) cells. This polymer has been shown to effectively kill cancer cells in-vitro, elicit an anti-tumor response in mice, and to increase damage associated molecular patterns (DAMPs) such as extracellular release of adenosine triphosphate (ATP) and the nuclear escape of high mobility group protein B1 (HMGB1). Calreticulin (CRT), a surface marker of apoptotic and necrotic cancer cells that attracts macrophages, was studied to determine if PAHM can induce ICD. Indirect immunocytochemistry revealed that the untreated AsPC-1 cells exhibit an unusually high level of surface CRT, and that exposure to PAHM did not significantly impact CRT levels. This was further confirmed by flow cytometry, and is in line with similar literature studies. Further research is needed to confirm whether PAHM increases CRT levels in cancer cells, however they do not contradict previous studies investigating ICD. Further study of PAHM using a different cancer cell line may yield stronger results.