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Publication Date

Fall 2014

Degree Type

Thesis - Campus Access Only

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Tzvia Abramson

Keywords

antibody, CD20, CD47, SIRP

Subject Areas

Biology

Abstract

CD47 is a cell surface protein overexpressed by many cancer cells, relative to normal cells, and it interacts with ligand SIRPα expressed by phagocytic cells. The CD47-SIRPα interaction inhibits the phagocytosis of target cells and thus functions as an anti-phagocytic "don't eat me" signal thereby allowing cancer cells to escape elimination. Combination treatment of the anti-CD47 antibody synergizes with Rituximab, an anti-CD20 antibody, to eliminate B cell non-Hodgkin's lymphoma (NHL). Blocking the CD47-SIRPα interaction and engaging the Fc-receptor stimulates macrophages to engulf the cancer cells. However, anti-CD47 antibody has the potential to bind normal CD47-expressing cells. We hypothesized that co-targeting CD47 and CD20 using a single antibody molecule would increase selectivity to cancer cells and recapitulate the synergistic effect observed with combination therapies. We engineered a novel antibody composed of wild type SIRPα linked to Rituximab and showed binding and selectivity to dual expressing CD20+CD47+ cancer cells over single expressing CD47 red blood cells (RBCs). In addition, macrophages engulfed antibody coated cancer cells in vitro. Results from this study suggest our engineered antibody may serve as a potential therapeutic antibody that could selectively eliminate cancer cells in vivo.

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