Immunological Conversion of Solid Tumours Using a Bispecific Nanobioconjugate for Cancer Immunotherapy

Authors

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

Publication Date

12-1-2022

Journal

Nature Nanotechnology

Abstract

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.

Keywords

Humans, Membrane Proteins, Immunotherapy, Neoplasms, Phagocytosis

Comments

Supplementary Materials

PMID: 36357792