T Cell Delivery of Nanoparticles-Bound Anti-CD20 Monoclonal Antibody: Successful B Cell Depletion in the Spinal Cord during Experimental Autoimmune Encephalomyelitis

J Neuroimmune Pharmacol. 2021 Jun;16(2):376-389. doi: 10.1007/s11481-020-09931-w. Epub 2020 Jun 9.

Abstract

We developed a nanotechnology based-cell mediated drug delivery system by loading myelin antigen-specific T cells with nanoparticles bound to anti-CD20 monoclonal antibody. Anti-CD20 antibody is a current treatment (ocrelizumab) for multiple sclerosis (MS), a chronic, inflammatory and autoimmune disease of the central nervous system (CNS). CD20-depletion has been associated with efficacy in active relapsing and progressive MS, but may not efficiently target inflammatory cells compartmentalized in the CNS. In our work, the intravenous transfer of T cells containing nanoparticle-anti-CD20 complex in mice causes B cell depletion in the spleen and in the brain, whereas the injection of anti-CD20 alone depletes B cells only in the spleen. Testing this system in Experimental Autoimmune Encephalomyelitis (EAE), animal model of MS, we found that spinal cord B cell depletion ameliorates the disease course and pathology. Graphical Abstract.

Keywords: Anti-CD20; Drug delivery; EAE; Nanoparticles loaded T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antigens, CD20*
  • B-Lymphocytes*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Nanoparticle Drug Delivery System*
  • Peptide Fragments / immunology
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • T-Lymphocytes / transplantation*

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Myelin-Oligodendrocyte Glycoprotein
  • Nanoparticle Drug Delivery System
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)