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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
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

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.

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Acknowledgments

The author thanks Eva Guinan, Lee Nadler and Laurence Cooper. The author was funded by a Leukemia and Lymphoma Society Career Development Award and a New Investigator award from the American Society for Blood and Marrow Transplantation.

Conflict of interest

The author has no conflict of interest to report.

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Author notes

  1. Jeffrey K. Davies

    Present address: Centre for Haemato-Oncology, Barts Cancer Institute, John Vane Science Centre, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA

    Jeffrey K. Davies

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  1. Jeffrey K. Davies
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Correspondence to Jeffrey K. Davies.

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Davies, J.K. Costimulatory blockade with monoclonal antibodies to induce alloanergy in donor lymphocytes. Int J Hematol 93, 594–601 (2011). https://doi.org/10.1007/s12185-011-0819-6

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  • DOI: https://doi.org/10.1007/s12185-011-0819-6

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