Combination of anti-CD4 antibody treatment and donor lymphocyte infusion ameliorates graft-versus-host disease while preserving graft-versus-tumor effects in murine allogeneic hematopoietic stem cell transplantation

Cancer Sci. 2017 Oct;108(10):1967-1973. doi: 10.1111/cas.13346. Epub 2017 Aug 29.


Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not only a well-established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo-HSCT to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft-versus-host disease (GVHD). CD4+ T cells have been implicated in several aspects of GVHD, and suppress antitumor CD8+ T-cell responses. In the present study, we investigated clinically applicable allo-HSCT protocols designed to maximize antitumor effects while reducing the risk of GVHD. We used a mouse model of allo-HSCT with s.c. tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute GVHD. Early treatment with anti-CD4 mAb substantially ameliorated GVHD while preserving antitumor effects, leading to improved survival in myeloablative allo-HSCT. Late treatment with anti-CD4 mAb also ameliorated GVHD to some extent. Donor lymphocyte infusion in GVHD mice treated with anti-CD4 mAb further suppressed tumor growth without exacerbating GVHD. Collectively, our results suggest that myeloablative allo-HSCT followed by anti-CD4 mAb treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.

Keywords: Allogeneic hematopoietic stem cell transplantation; CD4; donor lymphocyte infusion; graft-versus-host disease; graft-versus-tumor.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacology
  • CD4 Antigens / immunology*
  • Cell Line, Tumor
  • Colonic Neoplasms / therapy*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / therapy*
  • Hematopoietic Stem Cell Transplantation / mortality*
  • Immunotherapy, Adoptive / methods
  • Lymphocyte Transfusion / methods*
  • Mice
  • Survival Analysis
  • Transplantation Conditioning
  • Transplantation, Homologous / mortality
  • Treatment Outcome


  • Antibodies, Monoclonal
  • CD4 Antigens