Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy

Autor: Song Shen, Cheng-Tao Jiang, Hua Huang, Jin-Zhi Du, Meng-Hua Xiong, Qian-Ni Ye, Ya-Nan Fan, Dong-Kun Zhao, Jun Wang, Kai-Ge Chen, Cong-Fei Xu, Xianzhu Yang, An Liu, Hou-Bing Zhang
Rok vydání: 2021
Předmět:
Cytotoxicity
Immunologic
Male
0301 basic medicine
medicine.drug_class
T-Lymphocytes
Science
medicine.medical_treatment
T cell
General Physics and Astronomy
CD8-Positive T-Lymphocytes
Monoclonal antibody
Article
General Biochemistry
Genetics and Molecular Biology
Natural killer cell
Immunomodulation
03 medical and health sciences
0302 clinical medicine
Immune system
Cancer immunotherapy
Cell Line
Tumor
Neoplasms
medicine
Animals
Multidisciplinary
biology
Chemistry
Immunity
Antibodies
Monoclonal
General Chemistry
Immunotherapy
Chimeric antigen receptor
Cell biology
Killer Cells
Natural
Mice
Inbred C57BL
Immobilized Proteins
030104 developmental biology
medicine.anatomical_structure
Nanotechnology in cancer
030220 oncology & carcinogenesis
Drug delivery
biology.protein
Nanoparticles
Female
Antibody
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
Nature Communications
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE
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