MULT1E/mIL-12: A Novel Bifunctional Protein for Natural Killer Cell Activation

Authors:

Mrs. Ashlee Tietje, Dr. Jinhua Li, Dr. Xianzhong Yu, Dr. Yanzhang Wei

PI/Advisor:

Dr. Yanzhang Wei

Program:

Biological Sciences (College of Agriculture, Forestry and Life Sciences)

Abstract:

Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors like NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce these ligands’ expression, leaving them less detectable by NK cells. Along with these receptors, NK cells also require activating cytokines, like IL-12. The goal of this study is to develop a novel bi-functional fusion protein for enhanced NK cell activation. The proposed protein combines the extracellular domain of the NKG2D ligand MULT1E and mouse IL-12. It is hypothesized that when expressed by tumor cells, the protein will activate NK and other killer cells using the NKG2D receptor, and deliver mIL-12 to the NK cells where it can interact with the IL-12R and enhance cytotoxicity. The fusion protein, when expressed by engineered tumor cells, indeed activated NK cells in vitro as assayed by increased production of INF-γ and cytotoxicity and significantly reduced tumor growth in vivo. Although the study is preliminary, the data suggest that the MULT1E/mIL-12 bi-functional fusion protein is an effective activator of NK cells for cancer treatment.

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