Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes

Blood. 2006 Feb 15;107(4):1564-9. doi: 10.1182/blood-2005-07-2738. Epub 2005 Oct 18.


A trifunctional bispecific antibody (BiLu) directed against murine CD3 and human epithelial-cell adhesion molecule (EpCAM) was tested for its ability to improve cell-mediated adoptive immunotherapy in a murine model of B16 melanoma cells transfected with human EpCAM. Intraperitoneal inoculation of naive C57BL/6 (C57) splenocytes induced lethal graft versus host disease (GVHD) in 85% to 97% of sublethally irradiated (BALB/c x C57BL/6) F1 (F1) hosts inoculated intraperitoneally with a sublethal or lethal dose of melanoma cells. BiLu antibodies given intraperitoneally concomitantly with alloreactive C57 cells effectively prevented GVHD-related and tumor-related death in 16 of 25 F1 mice inoculated with a sublethal tumor-cell dose and in 10 of 20 mice inoculated with a lethal tumor-cell dose over a follow-up period of more than 200 days. BiLu treatment also efficiently prevented severe GVHD, which was induced by high doses of BALB/c-derived splenocytes. Trifunctional bispecific antibodies (TbsAbs) capable of cross-linking T lymphocytes, natural killer, and other FcgammaR-positive effector cells, via their Fc region, to the tumor cells may be applied together with adoptive allogeneic-cell therapy to maximize antitumor responses while acting on GVHD in patients with minimal residual disease.

MeSH terms

  • Animals
  • Antibodies, Bispecific / therapeutic use*
  • Cell Adhesion Molecules / immunology
  • Female
  • Graft vs Host Disease / immunology*
  • Lymphocyte Transfusion*
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Transplantation, Homologous / immunology*


  • Antibodies, Bispecific
  • Cell Adhesion Molecules