Date of Award

2017

Document Type

Thesis

Degree Name

Bachelor of Arts (BA)

First Advisor

Dr. John Harms

Second Advisor

Dr. Lawrence Mylin

Abstract

Pancreatic cancer is aggressive and poorly understood with a five-year survival rate of only 9% because most cases are diagnosed at a late stage. Because of ambiguous symptoms, pancreatic cancer is very difficult to detect early, and often when it is finally diagnosed, the cancer has already metastasized or has become too robust to cure. Current treatments are largely ineffective, so there is a great need for a novel approach to targeting this debilitating disease. To determine whether an intracellular peptide target expressed only in pancreatic cancer cells can be utilized to control or eradicate pancreatic cancer tumors by T cell immunity, an altered form of the gastrin/cholecystokinin receptor (CCK2R) associated with aggressive pancreatic cancers was targeted. Altered splicing of the CCK2R mRNA encodes a variant receptor, CCK2i4SVR, which contains a 69 amino acid insertion within the third intracellular loop.Our group has shown that a synthetic peptide corresponding to twenty amino acids of the loop elicits a T cell response in mice. The goal of this research was to determine whether murine cells hyper-expressing the intron-containing CCK2i4SVR variant could elicit similar T cell responses.To achieve particularly high levels of receptor,CCK2i4SVR was transiently transfected by an optimized method intomurine pancreatic cancercells that already expressed a basal amount of the human,variant receptor, and, 48 hours later,these cells were irradiated and used to immunize C57Bl/6 mice. Intron-specific T cell responses were monitored by ELISPOT, and it was unclear whether the super-transfected cells elicited an intron-specific T cell response.

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