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An immune edited tumour versus a tumour edited immune system: prospects for immune therapy of acute myeloid leukaemia

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Abstract

Cell based therapies for acute myeloid leukaemia (AML) have made significant progress in the last decade benefiting the prognosis and survival of patients with this aggressive form of leukaemia. Due to advances in haematopoietic stem cell transplantation (HSCT) and particularly the advent of reduced intensity conditioning (RIC), the scope of transplantation has now extended to those patients previously ineligible due to age and health restrictions and has been associated with a decrease in transplant related mortality. The apparent graft versus leukaemia (GvL) effect observed following HSCT demonstrates the potential of the immune system to target and eradicate AML cells. Building on previously published pre-clinical studies by ourselves and others, we are now initiating a Phase I clinical study in which lentiviral vectors are used to genetically modify AML cells to express B7.1 (CD80) and IL-2. By combining allogeneic HSCT with immunisation, using the autologous AML cells expressing B7.1 and IL-2, we hope to stimulate immune eradication of residual AML cells in poor prognosis patients that have achieved donor chimerism. In this report we describe the background to cell therapy based approaches for AML, and discuss difficulties associated with the deployment of a chronically stimulated, hence exhausted/depleted immune system to eradicate tumour cells that have already escaped immune surveillance.

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Abbreviations

HSCT:

Haematopoietic stem cell transplant

AML:

Acute myeloid leukaemia

GvL:

Graft versus leukaemia

DLI:

Donor leukocyte infusion

VUD:

Volunteer unrelated donor

GvHD:

Graft versus host disease

MDS:

Myelodysplastic syndrome

RIC:

Reduced intensity conditioning

APC:

Antigen presenting cell

mHA:

Minor histocompatibility antigens

LD-DC:

Leukaemia derived-dendritic cell

CTL:

Cytotoxic T lymphocytes

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Acknowledgements

L.C. is funded by Elimination of Leukaemia Fund. N.R.H., J.G.-L. and B.G. are funded by Leukaemia Research Fund. The tumour immune therapy programme in this department is funded by grants from the UK Department of Health, Elimination of Leukaemia Fund, Leukaemia Research Fund, Rose Trees Trust, John and Holly Burton Myeloma Research Programme, Biotechnology & Biological Sciences Research Council (BBSRC), and the Engineering and Physical Sciences Research Council (EPSRC).

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Authors and Affiliations

  1. King’s College London, Department of Haematological Molecular Medicine, The Rayne Institute, 123 Coldharbour Lane, SE5 9NU, London, UK

    Lucas Chan, Nicola R. Hardwick, Barbara-ann Guinn, Dave Darling, Joop Gäken, Joanna Galea-Lauri, Aloysius Y. Ho, Ghulam J. Mufti & Farzin Farzaneh

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  1. Lucas Chan
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  2. Nicola R. Hardwick
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  3. Barbara-ann Guinn
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  4. Dave Darling
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  8. Ghulam J. Mufti
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  9. Farzin Farzaneh
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Correspondence to Farzin Farzaneh.

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This article is a symposium paper from the “Robert Baldwin Symposium: 50 years of Cancer Immunotherapy”, held in Nottingham, Great Britain, on 30th June 2005.

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Chan, L., Hardwick, N.R., Guinn, Ba. et al. An immune edited tumour versus a tumour edited immune system: prospects for immune therapy of acute myeloid leukaemia. Cancer Immunol Immunother 55, 1017–1024 (2006). https://doi.org/10.1007/s00262-006-0129-7

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