Development of therapeutic antibodies against SIRPα

• Main Author: Chan, Lynn Xing Hui
• Other Authors: Par Nordlund
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/71532
• Institution: Nanyang Technological University

Cancer can evade detection by the immune system through interactions with effector cells such as macrophages. CD47 acts as a “don’t eat me” signal for normal cells and is overexpressed in many cancer types. CD47 interacts with SIRPα on macrophages and inhibits phagocytosis. Disrupting the CD47-SIRPα signalling results in increased phagocytosis of cancerous cells. Most studies have so far focused on targeting CD47, however, its ubiquitous expression has raised concerns that such therapeutic agents could lead to unintended toxic effects. Also, the binding site of CD47 on SIRPα is a cryptic epitope, thus a small therapeutic agent is required to target it. To circumvent these issues, we focused on developing a small single VH domain antibody against SIRPα using a recombinant VH phage display library. Here, we have optimized biopanning strategies using different versions of SIRPα and different selection methods and have isolated a SIRPα binder that binds with low nanomolar affinity. The SIRPα binder identified through this research provides a functional basis for further modifications to improve its binding affinity with the ultimate aim of developing a therapeutic antibody against SIRPα.