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An Investigation of a Novel NKG2D Ligand-Targeting Fusion Protein with Potential as a Cancer Immunotherapeutic Agent

Flannery , Meghan Maureen
http://orcid.org/0000-0001-7317-1095
http://rave.ohiolink.edu/etdc/view?acc_num=osu1429286080

Abstract Details

2015, Master of Science, Ohio State University, Anatomy.
Cancer immunotherapy is a treatment approach aimed towards harnessing and enhancing the immune system’s intrinsic ability to eliminate malignant cells. One feature which lends to the attractiveness of cancer immunotherapy is the extensive capacity of the immune system to recognize specific molecular targets expressed on pathogenic or malignant cells. Natural-killer group 2, member D (NKG2D) ligands are “stress-induced” proteins which are not typically expressed in most normal, healthy tissues, but are upregulated in response to conditions of cellular stress, such as those arising from malignant transformation. These ligands have been shown to be widely expressed on a variety of cancer types, and thus, represent auspicious targets for the development of novel immunotherapies. To capitalize upon the tumor-specific expression of NKG2D ligands, a novel NKG2D ligand-targeting fusion protein was created, in which the extracellular domain of NKG2D, the receptor for NKG2D ligands, is fused to the Fc domain of human immunoglobulin G1 (IgG1). For this NKG2D-Fc fusion protein (NKG2D-Fc), the NKG2D region serves as the binding domain, intended to target NKG2D ligands expressed on tumor cells, while the Fc region serves as the effector domain, providing a site for interaction with various immune components which can mediate destruction of tumors. This thesis aims to describe this novel immunotherapeutic fusion protein and to examine its binding ability. NKG2D-Fc was hypothesized to be able to recognize and bind to NKG2D ligands expressed on human cancer cells. Results of flow cytometry analysis and ELISA demonstrated that NKG2D-Fc was able to bind to NKG2D ligands expressed on a human breast cancer cell line and a human melanoma cell line. These results are promising as they demonstrate that this novel construct can effectively bind to NKG2D ligands on cancer cells and warrant further investigation of this fusion protein as a potential cancer immunotherapeutic agent.
Amanda Agnew (Advisor)
Eileen Kalmar (Committee Member)
57 p.
Anatomy and Physiology; Medicine; Oncology
Immunotherapy; Cancer; NKG2D; Fusion Protein

Recommended Citations

Citations

  • Flannery , M. M. (2015). An Investigation of a Novel NKG2D Ligand-Targeting Fusion Protein with Potential as a Cancer Immunotherapeutic Agent [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429286080

    APA Style (7th edition)

  • Flannery , Meghan . An Investigation of a Novel NKG2D Ligand-Targeting Fusion Protein with Potential as a Cancer Immunotherapeutic Agent . 2015. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429286080.

    MLA Style (8th edition)

  • Flannery , Meghan . "An Investigation of a Novel NKG2D Ligand-Targeting Fusion Protein with Potential as a Cancer Immunotherapeutic Agent ." Master's thesis, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429286080

    Chicago Manual of Style (17th edition)

osu1429286080
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© 2015, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.