Utilizing Neoantigens to Reinforce the Immune Response in Cancer



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Oncolytic virotherapy is the genetic engineering of viruses to specifically target and lyse cancer cells. One approach to combating malignant cell growth is to target neoantigens, which are proteasome processed peptides that result from acquired mutations in cancerous cells. The resulting neoantigen will be presented on major histocompatibility complex (MHC) class I for the activation of immune cells, which will destroy any malignant cells containing the same neoantigen. The major goal of our project is to determine if oncolytic herpes simplex viruses developed in our lab can be used as a lytic agent to release neoantigens from individual patients without the need to identify and then deliver them. We intend to construct a model system by introducing the following two antigens into tumor cells. The first one is a specific mutated extracellular signal-regulated kinase 2 (ERK2), in which a single amino acid mutation creates an epitope that produces a significant killing response from cytotoxic T-cells. The second one is a particular immunogenic epitope on glycoprotein B (gB498-505) of HSV-1. To detect the expression of the gB and ERK2 epitopes, the construct was built to express a modified GFP (dGFP), which has a shorter half-life than wild-type GFP.