Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies

Abstract

Immunotherapy Packs a One-Two Punch Despite the immune system's best efforts, cancer always seems to be one step ahead. One example of this is that tumor cells express CD47 on their cell surface. CD47 acts as a “don't eat me” signal to phagocytic macrophages. A potential therapeutic strategy could thus be to block this signal. Weiskopf et al. (p. 88 , published online 30 May; see the Perspective by Kershaw and Smyth ) created variants of the CD47 receptor, SIRPα, that could act as high-affinity antagonists of CD47. Although the antagonists blocked CD47 effectively in tumor-bearing mice, on their own they did not induce macrophages to phagocytose the tumor cells. When paired with a variety of therapeutic antitumor antibodies, however, the CD47 antagonists were very effective in treating several mouse tumor models.