Shared Biology of GVHD and GVT Effects: Potential Methods of Separation

Crit Rev Oncol Hematol. 2006 Mar;57(3):225-44. doi: 10.1016/j.critrevonc.2005.07.001. Epub 2005 Oct 3.

Abstract

The difficult separation of clinical graft-versus-tumor (GVT) effects from graft-versus-host disease (GVHD) reflects their shared biology. Experimental approaches to mediate GVT effects while limiting GVHD include: (1) allograft T cell depletion followed by immune enhancement; (2) modulation of T cell dose or T cell subset composition; (3) donor lymphocyte infusion; (4) reduced-intensity host preparation; (5) modulation of Th1/Th2 and Tc1/Tc2 cell balance; (6) cytokine therapy or neutralization; (7) T regulatory cell therapy; (8) co-stimulatory pathway modulation; (9) chemokine pathway modulation; (10) induction of antigen-specific T cells; (11) alloreactive NK cell therapy; and (12) targeted pharmaceutical inhibition of proteosome, mammalian target of rapamycin, and histone deacetylase pathways. Clearly, a multitude of approaches exist that hold promise for separating GVT effects from GVHD. Future success in this endeavor will require a strong commitment towards translational research and continued advances in cell, vaccine, cytokine, monoclonal antibody, and targeted molecular therapy.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Drug Design
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Graft vs Host Disease* / immunology
  • Graft vs Host Disease* / therapy
  • Graft vs Tumor Effect* / immunology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / immunology
  • Humans
  • Immunotherapy*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation
  • Lymphocyte Depletion
  • Lymphocyte Transfusion
  • Male
  • Neoplasms* / complications
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Proteasome Endopeptidase Complex / immunology
  • Proteasome Inhibitors
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / transplantation
  • Transplantation, Homologous

Substances

  • Cytokines
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex
  • Histone Deacetylases