Cancer Therapy Targeting CD47/SIRPα

SIMPLE SUMMARY: The interaction between cluster of differentiation 47 (CD47) on cancer cells and signal regulatory protein alpha (SIRPα) on immune cells, such as macrophages and dendritic cells, generates a “don’t eat me” signal. This is a common mechanism that provides cancer cells an escape from the innate immune system. Several therapeutics directed to CD47 or SIRPα have entered early clinical trials in recent years. In this article, we review the role of CD47/SIRPα axis in cancer, and summarize the literature on the efficacy and safety of therapeutics targeting CD47 or SIRPα. We also discuss the future implementation of these therapeutics in the treatments of various cancer types. ABSTRACT: In the past decade, the field of cancer immunotherapy has rapidly advanced, establishing a crucial role for immune checkpoint blockers in the treatment of a variety of cancer types. In parallel with these remarkable clinical developments, further efforts have focused on ways of unleashing adaptive immune responses against cancer. CD47, a cell surface molecule overexpressed by several cancer types that facilitates immune escape from macrophages, dendritic cells and natural killer cells, and its ligand SIRPα, have emerged as potential therapeutic targets. A number of agents directed to CD47/SIRPα have been developed and demonstrated preclinical activity. Early phase clinical trials are investigating CD47/SIRPα directed agents with available data, suggesting safety and preliminary activity. Herein, we provide an overview of the mechanistic rationale of targeting CD47/SIRPα axis and associated clinical evidence.