PMID- 23752205
OWN - NLM
STAT- MEDLINE
DCOM- 20131112
LR  - 20211021
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 9
DP  - 2013 Sep
TI  - Synthetic HLA-G proteins for therapeutic use in transplantation.
PG  - 3643-51
LID - 10.1096/fj.13-228247 [doi]
AB  - 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: (alpha3-L)x2 and (alpha1-alpha3)x2 polypeptides. We show their capability to bind 
      the HLA-G receptor LILRB2 and their functions in vitro and in vivo. The (alpha1-alpha3)x2 
      polypeptide proved to be a potent tolerogenic molecule in vivo: One treatment of 
      skin allograft recipient mice with (alpha1-alpha3)x2 was sufficient to significantly 
      prolong graft survival, and four weekly treatments induced complete tolerance. 
      Furthermore, (alpha1-alpha3)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 (alpha1-alpha3)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.
FAU - LeMaoult, Joel
AU  - LeMaoult J
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Institute 
      of Emerging Diseases and Innovative Therapies (iMETI), Research Division in 
      Hematology and Immunology (SRHI), Paris, France. joel.lemaoult@cea.fr
FAU - Daouya, Marina
AU  - Daouya M
FAU - Wu, Juan
AU  - Wu J
FAU - Loustau, Maria
AU  - Loustau M
FAU - Horuzsko, Anatolij
AU  - Horuzsko A
FAU - Carosella, Edgardo D
AU  - Carosella ED
LA  - eng
GR  - R56 AI055923/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130610
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (HLA-G Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Flow Cytometry
MH  - Graft Survival/drug effects
MH  - HLA-G Antigens/*chemistry/pharmacology/*therapeutic use
MH  - Humans
MH  - Mice
MH  - Peptides/chemistry/pharmacology/therapeutic use
MH  - Transplantation, Homologous
PMC - PMC3752534
OTO - NOTNLM
OT  - engineered molecules
OT  - immune regulation
OT  - therapy
OT  - tolerance
EDAT- 2013/06/12 06:00
MHDA- 2013/11/13 06:00
PMCR- 2014/09/01
CRDT- 2013/06/12 06:00
PHST- 2013/06/12 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2013/11/13 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - fj.13-228247 [pii]
AID - 13-228247 [pii]
AID - 10.1096/fj.13-228247 [doi]
PST - ppublish
SO  - FASEB J. 2013 Sep;27(9):3643-51. doi: 10.1096/fj.13-228247. Epub 2013 Jun 10.