Improving treatment of solid cancers by nanoconjugate-mediated immune conversion of tumour cells

Solid tumours display limited response to immunotherapies. By contrast, hematological malignancies exhibit significantly higher response rates to immunotherapies as compared to solid tumors. Among several microenvironmental and biological disparities, the differential expression of unique immune regulatory molecules significantly contributes to the blood cancer’s interaction with immune cells. The self-ligand receptor of the signaling lymphocytic activation molecule family member 7 (SLAMF7), a molecule that is critical in promoting the body’s innate immune cell to detect and engulf cancer cells, is expressed nearly exclusively on the cell surface of hematologic tumours, but not on solid ones. Here, we show that a bispecific nanobioconjugate that decorates SLAMF7 onto the surface of solid tumours induces robust phagocytosis and activates phagocytes cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, sensitising the tumours to immune checkpoint blockade. Our findings support an immunological conversion strategy that employs nano-adjuvants to improve the effectiveness of immunotherapies for solid tumours.