Development of a lectin-Fc fusion protein with antiviral and anti-cancer activity.

Author

Matthew William Dent, University of LouisvilleFollow

Date on Master's Thesis/Doctoral Dissertation

5-2019

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Matoba, Nobuyuki

Committee Co-Chair (if applicable)

Palmer, Kenneth

Committee Member

Palmer, Kenneth

Committee Member

Telang, Sucheta

Committee Member

Yan, Jun

Committee Member

Miller, Donald

Author's Keywords

HIV; biotechnology; drug development; lectin; antibody; plant-based protein expression

Abstract

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell surface receptors and is capable of protecting mice against lung and flank B16F10 challenges primarily through Fc-mediated mechanisms. This work builds upon the framework developed by our group supporting the preclinical development of AvFc as a novel antiviral and anti-cancer protein.

Recommended Citation

Dent, Matthew William, "Development of a lectin-Fc fusion protein with antiviral and anti-cancer activity." (2019). Electronic Theses and Dissertations. Paper 3237.
https://doi.org/10.18297/etd/3237