Frontiers in Immunology (Mar 2024)

Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells

  • Lucille Lamendour,
  • Mäelle Gilotin,
  • Nora Deluce-Kakwata Nkor,
  • Zineb Lakhrif,
  • Daniel Meley,
  • Anne Poupon,
  • Anne Poupon,
  • Thibaut Laboute,
  • Anne di Tommaso,
  • Jean-Jacques Pin,
  • Denis Mulleman,
  • Denis Mulleman,
  • Guillaume Le Mélédo,
  • Guillaume Le Mélédo,
  • Nicolas Aubrey,
  • Hervé Watier,
  • Florence Velge-Roussel

DOI
https://doi.org/10.3389/fimmu.2024.1369117
Journal volume & issue
Vol. 15

Abstract

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There is an urgent need for alternative therapies targeting human dendritic cells (DCs) that could reverse inflammatory syndromes in many autoimmune and inflammatory diseases and organ transplantations. Here, we describe a bispecific antibody (bsAb) strategy tethering two pathogen-recognition receptors at the surface of human DCs. This cross-linking switches DCs into a tolerant profile able to induce regulatory T-cell differentiation. The bsAbs, not parental Abs, induced interleukin 10 and transforming growth factor β1 secretion in monocyte-derived DCs and human peripheral blood mononuclear cells. In addition, they induced interleukin 10 secretion by synovial fluid cells in rheumatoid arthritis and gout patients. This concept of bsAb-induced tethering of surface pathogen-recognition receptors switching cell properties opens a new therapeutic avenue for controlling inflammation and restoring immune tolerance.

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