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British Journal of Cancer (2005) 93, 1085–1091. doi:10.1038/sj.bjc.6602839 www.bjcancer.com
Published online 25 October 2005
Engineering T cells for cancer therapy
W Mansoor1, D E Gilham1, F C Thistlethwaite1 and R E Hawkins1
1Cancer Research UK, Department of Medical Oncology, University of Manchester, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK
Correspondence: Professor RE Hawkins, E-mail: robert.e.hawkins@manchester.ac.uk
Received 20 April 2005; Revised 1 September 2005; Accepted 7 September 2005; Published online 25 October 2005.
Abstract
It is generally accepted that the immune system plays an important role in controlling tumour development. However, the interplay between tumour and immune system is complex, as demonstrated by the fact that tumours can successfully establish and develop despite the presence of T cells in tumour. An improved understanding of how tumours evade T-cell surveillance, coupled with technical developments allowing the culture and manipulation of T cells, has driven the exploration of therapeutic strategies based on the adoptive transfer of tumour-specific T cells. The isolation, expansion and re-infusion of large numbers of tumour-specific T cells generated from tumour biopsies has been shown to be feasible. Indeed, impressive clinical responses have been documented in melanoma patients treated with these T cells. These studies and others demonstrate the potential of T cells for the adoptive therapy of cancer. However, the significant technical issues relating to the production of natural tumour-specific T cells suggest that the application of this approach is likely to be limited at the moment. With the advent of retroviral gene transfer technology, it has become possible to efficiently endow T cells with antigen-specific receptors. Using this strategy, it is potentially possible to generate large numbers of tumour reactive T cells rapidly. This review summarises the current gene therapy approaches in relation to the development of adoptive T-cell-based cancer treatments, as these methods now head towards testing in the clinical trial setting.
Keywords:
chimeric immune receptor, antibody
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