Efficacy of pretreatment of allografts with methoxypolyethylene glycol-succinimidyl-propionic acid ester in combination with an anti-OX40L monoclonal antibody in relieving graft-versus-host disease in mice

Int J Hematol. 2010 Nov;92(4):609-16. doi: 10.1007/s12185-010-0701-y. Epub 2010 Oct 17.


We designed to determine whether pretreatment of allografts with methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and an anti-OX40L monoclonal antibody (McAb) can relieve acute graft-versus-host disease in allogeneic bone marrow transplantation recipients. Responder splenocytes from C57BL/6 donor mice were incubated with stimulator splenocytes from BALB/c recipient mice for 7 days in the presence or absence of anti-OX40L McAb followed by mPEG-SPA modification. Donor BM cells plus mixed culture T cells were then transplanted into myeloablatively irradiated BALB/c mice. The signs of GVHD were less evident in mice of groups B (mPEG-SPA modification group), C (anti-OX40L McAb pretreated group) and D (dual-treated group), with average survival durations all longer than those in group A (non-treated BMT group) (P < 0.05). The survival rates on day 60 post-BMT in groups B, C and D were 50, 41.7 and 66.7%, respectively. After BMT, serum IL-4 and IL-10 levels elevated in groups B, C (P < 0.05) and even more significantly increased in group D (P < 0.01), while serum IFN-gamma levels decreased in these three groups (P < 0.01). In conclusion, the combination of mPEG-SPA and anti-OX40L McAb can block T cell-activated antigens, co-stimulatory pathways and induce the immune shift of Th cells toward Th2 cells; their effects in ameliorating GVHD are synergistic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Bone Marrow Transplantation*
  • Cytokines / blood
  • Female
  • Graft Enhancement, Immunologic / methods*
  • Graft vs Host Disease / prevention & control*
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • OX40 Ligand
  • Polyethylene Glycols / therapeutic use*
  • Spleen / cytology*
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology
  • Transplantation, Homologous
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors / immunology*


  • Antibodies, Monoclonal
  • Cytokines
  • Membrane Glycoproteins
  • OX40 Ligand
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors
  • methoxypolyethylene glycol-succinimidyl-propionic acid ester
  • Polyethylene Glycols