Nanovesicles released by OKT3 hybridoma express fully active antibodies

J Enzyme Inhib Med Chem. 2021 Dec;36(1):175-182. doi: 10.1080/14756366.2020.1852401.

Abstract

Recent findings have shown that nanovesicles preparations from either primary immune cells culture supernatants or plasma contain immunoglobulins, suggesting that a natural way of antibody production may be through exosome release. To verify this hypothesis, we used the OKT3 hybridoma clone, which produces a murine IgG2a monoclonal antibody used to reduce rejection in patients undergoing organ transplantation. We showed exosome-associated immunoglobulins in hybridoma supernatants, by Western blot, nanoscale flow cytometry and immunocapture-based ELISA. The OKT3-exo was also being able to trigger cytokines production in both CD4 and CD8 T cells. These results show that nanovesicles contain immunoglobulin and could be used for immunotherapy. These data could lead to a new approach to improve the effectiveness of therapeutic antibodies by exploiting their natural property to be expressed on nanovesicle membrane, that probably render them more stable and as a consequence more capable to interact with their specific ligand in the best way.

Keywords: Exosomes; OKT3 hybridoma cell line; extracellular vesicles; immunoglobulins.

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Exosomes / chemistry
  • Exosomes / genetics
  • Exosomes / immunology*
  • Gene Expression
  • Humans
  • Hybridomas / chemistry
  • Hybridomas / immunology*
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / immunology
  • Lymphocyte Activation
  • Macrophages / cytology
  • Macrophages / immunology
  • Mice
  • Multiple Myeloma / immunology
  • Muromonab-CD3 / genetics
  • Muromonab-CD3 / immunology*
  • Neoplasms, Experimental / immunology
  • Primary Cell Culture
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Surface
  • CD3 Complex
  • Cytokines
  • Immunoglobulin G
  • Muromonab-CD3