Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy

Cheng-Tao Jiang, Kai-Ge Chen, An Liu, Hua Huang, Ya-Nan Fan, Dong-Kun Zhao, Qian-Ni Ye, Hou-Bing Zhang, Cong-Fei Xu, Song Shen (), Meng-Hua Xiong, Jin-Zhi Du, Xian-Zhu Yang and Jun Wang ()
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Cheng-Tao Jiang: Guangzhou International Campus
Kai-Ge Chen: University of Science and Technology of China
An Liu: University of Science and Technology of China
Hua Huang: Guangzhou International Campus
Ya-Nan Fan: Guangzhou International Campus
Dong-Kun Zhao: Guangzhou International Campus
Qian-Ni Ye: Guangzhou International Campus
Hou-Bing Zhang: Guangzhou International Campus
Cong-Fei Xu: Guangzhou International Campus
Song Shen: Guangzhou International Campus
Meng-Hua Xiong: Guangzhou International Campus
Jin-Zhi Du: Guangzhou International Campus
Xian-Zhu Yang: Guangzhou International Campus
Jun Wang: Guangzhou International Campus

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-21497-6

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