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

22 Citations (Scopus)

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

Fingerprint

Therapeutic Uses
HLA Antigens
GTP-Binding Proteins
Transplantation
Molecules
Peptides
Allografts
Antigen Receptors
Graft Survival
Tumor Cell Line
Grafts
Tumors
Skin
Cells
Engineers

Keywords

  • Engineered molecules
  • Immune regulation
  • Therapy
  • Tolerance

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Synthetic HLA-G proteins for therapeutic use in transplantation. / LeMaoult, Joel; Daouya, Marina; Wu, Juan; Loustau, Maria; Horuzsko, Anatolij; Carosella, Edgardo D.

In: FASEB Journal, Vol. 27, No. 9, 01.09.2013, p. 3643-3651.

Research output: Contribution to journalArticle

LeMaoult, J, Daouya, M, Wu, J, Loustau, M, Horuzsko, A & Carosella, ED 2013, 'Synthetic HLA-G proteins for therapeutic use in transplantation', FASEB Journal, vol. 27, no. 9, pp. 3643-3651. https://doi.org/10.1096/fj.13-228247
LeMaoult, Joel ; Daouya, Marina ; Wu, Juan ; Loustau, Maria ; Horuzsko, Anatolij ; Carosella, Edgardo D. / Synthetic HLA-G proteins for therapeutic use in transplantation. In: FASEB Journal. 2013 ; Vol. 27, No. 9. pp. 3643-3651.
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