Date of Award

5-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Biological Sciences

Committee Member

Dr. Yanzhang Wei, Committee Chair

Committee Member

Dr. Charlie Rice

Committee Member

Dr. Jeremy Tzeng

Committee Member

Dr. Xianzhong Yu

Abstract

Cancer is the second leading cause of disease death worldwide. Whereas cancer immunotherapy with cytokines in previous researches demonstrated effective in activating immune response against tumor cells, one major obstacle with the use of these cytokines is their severe side effects when delivered systemically at high doses. Another challenge is that tumor cells often lead to immune destruction by evading immunosurveillance of the innate immune system such as natural killer (NK) cells as well as of the Fas-mediated apoptosis by down-regulating their expression. In the present study, a novel fusion protein-IL-12/FasTI, consisting of mIL-12 and the transmembrane and intracellular domains of Fas, was successfully created. The fusion construct (pmIL-12/FasTI) in an expressing vector was transfected into the mouse pulmonary carcinoma cell line TC-1 and stable cell clones expressing the fusion protein were selected. In vitro studies confirmed the functions of the bifunctional protein as the induction of apoptosis of tumor cells and NK cell activation by increased IFN-γ production and cytotoxicity. This new approach may generate a promising therapeutic agent for tumor treatment when combined with tumor cell-specific gene delivery vehicles such as nanoparticles.

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