Synthetic HLA-G proteins for therapeutic use in transplantation

Joel LeMaoult, Marina Daouya, Juan Wu, Maria Loustau, Anatolij Horuzsko, Edgardo D. Carosella

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The human leukocyte antigen (HLA)-G is a tolerogenic molecule, whose expression by allografts is associated with better acceptance. An increasing interest in producing HLA-G as a clinical-grade molecule for therapy use is impaired by its complexity and limited stability. Our purpose was to engineer simpler and more stable HLA-G-derived molecules than the full-length HLA-G trimolecular complex that are also tolerogenic, functional as soluble molecules, and compatible with good manufacturing practice (GMP) production conditions. We present two synthetic molecules: (α3-L)x2 and (α13)x2 polypeptides. We show their capability to bind the HLA-G receptor LILRB2 and their functions in vitro and in vivo. The (α13)x2 polypeptide proved to be a potent tolerogenic molecule in vivo: One treatment of skin allograft recipient mice with (α13) x2 was sufficient to significantly prolong graft survival, and four weekly treatments induced complete tolerance. Furthermore, (α1- α3)x2 was active as a soluble molecule and capable of inhibiting the proliferation of tumor cell lines, as does the full length HLA-G trimolecular complex. Thus, the synthetic (α1- α3)x2 polypeptide is a stable and simpler alternative to the full-length HLA-G molecule. It can be produced under GMP conditions, it functions as a soluble molecule, and it is at least as tolerogenic as HLA-G in vivo.-LeMaoult, J., Daouya, M., Wu, J., Loustau, M., Horuzsko, A., Carosella, E. D. Synthetic HLA-G proteins for therapeutic use in transplantation.

Original languageEnglish (US)
Pages (from-to)3643-3651
Number of pages9
JournalFASEB Journal
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2013

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Keywords

  • Engineered molecules
  • Immune regulation
  • Therapy
  • Tolerance

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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