Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Biological Sciences


Yanzhang Wei

Committee Member

Lisa Bain

Committee Member

Charles Rice

Committee Member

Xianzhong Yu


One of the characteristics of advanced tumors is the evasion of the immune system. There are multiple methods that tumor cells employ to achieve this including reducing the expression of activating ligands on the cell surface and a shift in the tumor microenvironment toward pro-tumor cytokines. The purpose of this research is to develop a novel bifunctional fusion protein that will target these two deficiencies in the tumor microenvironment and activate killer cells that are already present. The proposed protein combines the extracellular domain of a ligand for the killer cell activating receptor NKG2D and Interleukin-12 (IL-12). It is hypothesized that when expressed by tumor cells by gene therapy, the protein will simultaneously activate NK and other killer cells using the NKG2D receptor, and deliver a locally high dose of IL-12 to the tumor microenvironment where it can interact with the IL-12 receptor and enhance cytotoxicity.