Date of Award

12-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Member

Dr. Yanzhang Wei, Committee Chair

Committee Member

Dr. Charlie Rice

Committee Member

Dr. Xianzhong Yu

Abstract

Cancer remains a major health issue worldwide, and the leading cause of death in nearly half the states in America. As our understanding of the immune system has improved, so too has our ability to create and tailor immunotherapy and gene therapy for cancer treatment. Therapy with cytokines to boost immune activity against cancer cells has had limited success, but is largely restrained by the toxicity of systemic administration of the high doses needed to elicit the desired effect. Also limiting the effect of such cytokine therapy is the issue of cancerous cells already implementing tactics to evade immune detection, so increasing immune activity may still not wholly eliminate those cancerous cells. In the present study, a humanized fusion protein, IL-12/hFasTI, consisting of murine IL-12 (biologically active as an activator of human NK cells) and the transmembrane and intracellular domains of human Fas, was successfully created. The fusion gene was transfected into the human cell lines HEK293 and HeLa, and stable fusion-gene expressing clones were produced and verified by RT-PCR and immunohistochemistry. Preliminary data also show that the fusion protein is able to activate human NK cells and human peripheral blood mononuclear cells (PBMCs). When functionally confirmed in animal models, it may well provide a promising potential for a therapy applicable to many cancer types when coupled with a tumor-cell specific delivery system like nanoparticles or CRISPR/Cas9 technology.

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