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Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-21497-6

2041-1723

Cheng‐Tao Jiang, Kaige Chen, An Liu, Hua Huang, Ya-Nan Fan, Dong‐Kun Zhao, Qian‐Ni Ye, Houbing Zhang, Cong‐Fei Xu, Song Shen, Menghua Xiong, Jin‐Zhi Du, Xianzhu Yang, Jun Wang,

Immunotherapy and Immune Responses

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.