Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy

• Published in: Nature communications Vol. 12; no. 1; pp. 1359 - 14
• Main Authors: Jiang, Cheng-Tao, Chen, Kai-Ge, Liu, An, Huang, Hua, Fan, Ya-Nan, Zhao, Dong-Kun, Ye, Qian-Ni, Zhang, Hou-Bing, Xu, Cong-Fei, Shen, Song, Xiong, Meng-Hua, Du, Jin-Zhi, Yang, Xian-Zhu, Wang, Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 639/925/352/152; 639/925/352/2733; Adapters; Adaptor proteins; Animal models; Animals; Antibodies; Antibodies, Monoclonal - metabolism; Antigens; Antitumor activity; Bispecific antibodies; Bridge maintenance; Cancer; Cancer immunotherapy; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Chemical reactions; Chimeric antigen receptors; Cytotoxicity, Immunologic; Effector cells; Female; Humanities and Social Sciences; Immobilization; Immobilized Proteins - metabolism; Immune checkpoint inhibitors; Immune response; Immune system; Immunity; Immunoglobulin G; Immunomodulation; Immunotherapy; Killer Cells, Natural - immunology; Lymphocytes; Lymphocytes T; Macrophages; Male; Mice; Mice, Inbred C57BL; Monoclonal antibodies; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Natural killer cells; Neoplasms - immunology; Neoplasms - therapy; Science; Science (multidisciplinary); T-Lymphocytes - immunology; Tumor cells
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21497-6

Modulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an ‘adaptor’ while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models. Current strategies to boost anti-tumor immune response include the use of immune checkpoint inhibitors and bispecific T cell-engaging antibodies. Here the authors describe a versatile antibody immobilization nanoplatform that can be used to deliver different combinations of immunotherapeutics, showing therapeutic superiority in pre-clinical models.