Improving TCR Gene Therapy for Treatment of Haematological Malignancies.pdfVIP

Hindawi Publishing Corporation Advances in Hematology Volume 2012, Article ID 404081, 11 pages doi:10.1155/2012/404081 Review Article Improving TCR Gene Therapy for Treatment of Haematological Malignancies Emma Nicholson, Sara Ghorashian, and Hans Stauss Department of Immunology, Royal Free Hospital, University College London, Hampstead Campus, Rowland Hill Street, London NW3 2QG3, UK Correspondence should be addressed to Emma Nicholson, e.nicholson@ucl.ac.uk Received 19 July 2011; Accepted 10 October 2011 Academic Editor: Shaji Kumar Copyright © 2012 Emma Nicholson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Adoptive immunotherapy using TCR gene modified T cells may allow separation of beneficial Graft versus tumour responses from harmful GvHD. Improvements to this include methods to generate high avidity or high affinity TCR, improvements in vector design and reduction in mispairing. Following adoptive transfer, TCR transduced T cells must be able to survive and persist in vivo to give most effective antitumour responses. Central memory or naive T cells have both been shown to be more effective than effector cells at expanding and persisting in vivo. Lymphodepletion may enhance persistence of transferred T cell populations. TCR gene transfer can be used to redirect CD4 helper T cells, and these could be used in combination with CD8+ tumour specific T cells to provide help for the antitumour response. Antigen specific T regulatory T cells can also be generated by TCR gene transfer and could be used to suppress unwanted alloresponses. 1. Introduction