FIGURE 2.

Combinatory strategies that improve the therapeutic effect of CD47‐signal regulatory protein alpha (SIRPα) blocking. Currently, five different strategies to improve CD47 blocking therapy are being evaluated. (1) In clinical trials with several different types of cancer parents, Fc receptor (FcR) crosslinking antibodies that directly target tumour antigens are combined with CD47 blocking. The combination of CD47 blocking with (5) stimulation of adaptive costimulatory signals or (2) blockade of adaptive ‘don't eat me’ signals is also a promising combinatory strategy, as increasing evidence states that the adaptive immune system has a pivotal role in the effect of CD47 blocking therapy. (3) The combination of anthracycline, epigenetic drugs (demethylating agents) and proteasome inhibitors also improved the therapeutic effect of CD47 blockade. Most likely, this improvement is at least partly caused by upregulation of ‘eat me’ signals on tumour cells triggering phagocytosis by immune cells. Finally, accumulating evidence points to CD47‐SIRPα blocking antibodies triggering not only phagocytosis but also autophagy of tumour cells and health issues. (4). Combination with autophagy blockers seems to improve the phagocytic index in non‐small cell lung cancer (NSCLC) and glioblastoma in a preclinical setting