On the mechanism of CD47 targeting in cancer

The report by Willingham et al. (1) is the most recent in a series of publications from the same group, in which the interaction between the broadly expressed surface molecule CD47 and the myeloid inhibitory receptor SIRPα was implicated as a potential therapeutic target in a variety of malignancies. The authors used xenotransplantation models in which various human solid tumor cells were engrafted into immunocompromised mice, and showed that cancer growth and metastasis were inhibited by antibodies against human CD47 that block interactions with SIRPα, but not by nonblocking anti-CD47 antibodies. In similarly designed studies they had already demonstrated elimination of various hematopoietic malignancies with the blocking anti-CD47 antibody and also that anti-CD47 treatment synergizes with the therapeutic anti-CD20 antibody Rituximab in non-Hodgkin lymphoma. They suggested that targeting of CD47-SIRPα interactions, either in the absence or in the presence of a cancer therapeutic antibody such as Rituximab, facilitates the eradication of tumor cells by promoting their phagocytic clearance by macrophages (1).