Date of Award

5-2010

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Microbiology

Advisor

Wei, Yanzhang

Committee Member

Scott , Tom

Committee Member

Yu , Xianzhong

Abstract

A growing body of evidence indicates that natural killer (NK) cells are paramount to the identification and elimination of cancerous and pre-cancerous cells during normal immunosurveillance. In addition, NK cells provide a vital link between the innate and adaptive immune systems during an anti-tumoral response. In the present study, a novel fusion protein was designed from the extracellular portion of mouse UL16-binding protein-like transcript 1 (MULT1), a ligand for the activating NKG2D receptor on NK cells, and a short arginine-glycine-aspartic acid (RGD) -containing peptide, which binds the integrin αvβ3 of tumor-specific neovasculature. In vitro studies showed that the fusion protein gene can be successfully incorporated into the genome of B16 mouse melanoma cells, it can be transcribed and translated efficiently, and it is appropriately secreted into the extracellular milieu. In vitro studies also showed that the MULT1E-RGD fusion protein successfully binds the integrin αvβ3, and transfection with the gene does not affected cell growth in B16 cells. In vivo studies indicate that transfected cancer cells, when injected subcutaneously in C57BL mice, take on a new phenotype and a slightly different growth pattern, consistent with an upregulated immune response to the tumor.

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Cell Biology Commons

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