Monocytes engineered with iSNAP inhibit human B-lymphoma progression

Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47-SIRP alpha recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has been well-known as the Don't eat me signal. By using an approach of integrated sensing and activating proteins (iSNAPs), we have rewired the CD47-SIRP alpha axis to create iSNAP-M which activates pathways in engineered human monocytes (iSNAP-MC). The mRNA expression levels of the monocyte/macrophage markers CD11b, CD14, and CD31 are upregulated in iSNAP-monocytes (iSNAP-MC). With PMA induction, the iSNAP-MC-derived macrophages (iSNAP-M phi) showed upregelation in CD86 and CD80, but not CD206. TNF alpha expression and secretion were also increased in iSNAP-M phi. Furthermore, the injection of iSNAP-MC into mice bearing human B-lymphoma tumors led to the suppression of tumor progression. Therefore, the engineered monocytes, via blockage of coinhibitory immune signals by rewiring CD47-SIRP alpha axis, can be applied to suppress target tumors for cancer immunotherapy.

Automated summary

The CD47-SIRP alpha axis has been rewired to create iSNAP-M, which activates engineered monocytes to suppress tumor progression.