Date on Master's Thesis/Doctoral Dissertation

5-2024

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)

Siskind, Leah

Committee Member

Siskind, Leah

Committee Member

Palmer, Kenneth

Committee Member

Kakar, Sham

Committee Member

Telang, Sucheta

Committee Member

Yaddanapudi, Kavitha

Author's Keywords

drug development; plant-made pharmaceuticals; cancer glycosylation; lectin; antibody; immunotherapy

Abstract

This thesis describes the investigation of Avaren-Fc (AvFc), a novel lectin-based therapeutic fusion protein consisting of the recombinant Avaren lectin and the Fc region of human IgG1, against ovarian cancer. AvFc possesses selectivity toward tumor associated N-linked high-mannose-type glycans. The present study demonstrates AvFc’s in vitro activity against OVCA cell lines via antibody-dependent cell-mediated cytotoxicity and its ability to extend the survival of mice challenged with murine ID8 OVCA cells after repeated systemic administration. Furthermore, AvFc treatment in this model was found to increase the presence of peritoneal leukocytes, suggesting a shift toward an improved antitumor immune response. Another key finding of the current work was AvFc’s preferential binding to primary human OVCA tumor tissue over healthy adjacent tissue. Overall, these results emphasize AvFc’s therapeutic potential by effectively leveraging OVCA-associated high-mannose glycans as a target to induce cancer cell elimination.

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