Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy

Nat Commun. 2021 Mar 1;12(1):1359. doi: 10.1038/s41467-021-21497-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Female
  • Immobilized Proteins / metabolism
  • Immunity
  • Immunomodulation*
  • Immunotherapy*
  • Killer Cells, Natural / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal
  • Immobilized Proteins