Costimulatory blockade with monoclonal antibodies to induce alloanergy in donor lymphocytes

Progress in Hematology Role of monoclonal antibodies for the prevention and treatment of graft-versus-host disease

DOI: 10.1007/s12185-011-0819-6

Cite this article as:
Davies, J.K. Int J Hematol (2011) 93: 594. doi:10.1007/s12185-011-0819-6

Abstract

Alloreactive donor T cells are central to the pathogenesis of Graft-versus-Host Disease (GvHD). Non-specific T cell depletion of donor grafts reduces GvHD, but increases infection and disease relapse. Several strategies are, therefore, in development to selectively remove alloreactive donor T cells prior to transplant while retaining beneficial donor T cells. An alternative approach is ex vivo alloanergization of donor T cells via allostimulation and blockade of costimulatory signals with fusion proteins or monoclonal antibodies. This strategy, which selectively inactivates alloreactive donor T cells, has been tested with some success in previous clinical trials of HLA-mismatched bone marrow transplantation. To build on the findings of these early trials, the strategy is now being tested in a multi-center clinical study of alloanergized donor lymphocyte infusion after HLA-mismatched stem cell transplantation. Recent advances in the understanding of alloanergization include the recognition of the central role played by CD4+ regulatory T cells and new applications include the combination of alloanergization with T cell redirection to maximize anti-tumor activity. This mini-review will give an overview of the immunological basis for alloanergization, the previous and current clinical applications, and how new pre-clinical data have helped to create exciting new avenues of translational research in this area.

Keywords

Allogeneic hematopoietic transplantation Graft-versus-Host Disease Costimulatory blockade Anergy Donor lymphocyte infusion 

Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  1. 1.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  2. 2.Centre for Haemato-Oncology, Barts Cancer Institute, John Vane Science CentreQueen Mary University of LondonLondonUK