期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-021-21497-6
关键词
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资金
- National Key R&D Program of China [2017YFA0205600]
- National Natural Science Foundation of China [51633008, 32071380, 31800831]
- Science and Technology Program of Guangzhou [007306355061]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S054]
- Guangdong Provincial Pearl River Talents Program [2017GC010713]
- Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) [2018GZR110102001]
The researchers developed a versatile antibody immobilization platform by conjugating antibodies onto nanoparticles, which effectively enhanced antitumor immune responses mediated by T cells, natural killer cells, and macrophages. This strategy shows promise in improving the efficacy of immunotherapy.
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 (alpha Fc) onto the nanoparticle surface (alpha Fc-NP), and confirm that alpha Fc-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.
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