Journal Article

Immunological conversion of solid tumours using a bispecific nanobioconjugate for cancer immunotherapy

Lu, Yifei, Huntoon, Kristin, Ha, JongHoon, Li, Jing, Zhao, Hai, Kim, Betty Y. S, Gallup, Thomas D, Yang, Zhaogang, Dong, Shiyan, Lee, DaeYong, Schrank, Benjamin R, Kang, Minjeong, Qie, Yaqing, Li, Xuefeng, Jiang, Wen, An, Yi, Wang, Yifan

2022

Overview

Solid tumours display a limited response to immunotherapies. By contrast, haematological malignancies exhibit significantly higher response rates to immunotherapies as compared with solid tumours. Among several microenvironmental and biological disparities, the differential expression of unique immune regulatory molecules contributes significantly to the interaction of blood cancer cells with immune cells. The self-ligand receptor of the signalling lymphocytic activation molecule family member 7 (SLAMF7), a molecule that is critical in promoting the body’s innate immune cells to detect and engulf cancer cells, is expressed nearly exclusively on the cell surface of haematologic tumours, but not on solid ones. Here we show that a bispecific nanobioconjugate that enables the decoration of SLAMF7 on the surface of solid tumours induces robust phagocytosis and activates the phagocyte cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS–STING) pathway, sensitizing the tumours to immune checkpoint blockade. Our findings support an immunological conversion strategy that uses nano-adjuvants to improve the effectiveness of immunotherapies for solid tumours.Solid tumours are less responsive to immunotherapies than haematological tumours due to specific biological differences. In this paper the authors propose a strategy to decorate the cell membrane of solid tumours with a protein typically present on haematological tumour cells that promotes phagocytosis of cancer cells, and show that this results in an increased immunotherapy efficacy in animal models of solid tumours.

• Publisher: Nature Publishing Group
• Subject: Adenosine monophosphate / Adjuvants / AMP / Animal models / Blood cancer / Cancer / Cancer immunotherapy / Cell activation / Cell membranes / Cell surface / Conversion / Cyclic GMP / Hematology / Immune checkpoint inhibitors / Immune system / Immunology / Immunotherapy / Interferon / Malignancy / Phagocytosis / Sensitizing / Signal transduction / Solid tumors / Stimulators / Tumors