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Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia

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Abstract

Immunotherapy is currently under active investigation as an adjuvant therapy to improve the overall survival of patients with acute myeloid leukaemia (AML) by eliminating residual leukaemic cells following standard therapy. The graft-versus-leukaemia effect observed following allogeneic haematopoietic stem cell transplantation has already demonstrated the significant role of immune cells in controlling AML, paving the way to further exploitation of this effect in optimized immunotherapy protocols. In this review, we discuss the current state of cellular immunotherapy as adjuvant therapy for AML, with a particular focus on new strategies and recently published results of preclinical and clinical studies. Therapeutic vaccines that are being tested in AML include whole tumour cells as an autologous source of multiple leukaemia-associated antigens (LAA) and autologous dendritic cells loaded with LAA as effective antigen-presenting cells. Furthermore, adoptive transfer of cytotoxic T cells or natural killer cells is under active investigation. Results from phase I and II trials are promising and support further investigation into the potential of cellular immunotherapeutic strategies to prevent or fight relapse in AML patients.

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Abbreviations

AML:

Acute myeloid leukaemia

CR:

Complete remission

CTL:

Cytotoxic T lymphocyte

DC:

Dendritic cell

DLI:

Donor leucocyte infusion

FAB:

French-American-British

GVHD:

Graft-versus-host-disease

GVL:

Graft-versus-leukaemia

HLA:

Human leucocyte antigen

HSCT:

Haematopoietic stem cell transplantation

LAA:

Leukaemia-associated antigen

LSA:

Leukaemia-specific antigen

mHAg:

Minor histocompatibility antigen

MHC:

Major histocompatibility complex

MRD:

Minimal residual disease

NK:

Natural killer

poly(I:C):

Polyinosinic polycytidylic acid

PR3:

Proteinase 3

RHAMM:

Receptor for hyaluronic acid-mediated motility

SSX2IP:

Synovial sarcoma X breakpoint 2-interacting protein

TAA:

Tumour-associated antigen

TLR:

Toll-like receptor

WHO:

World Health Organization

WT1:

Wilms’ tumour protein

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Acknowledgments

E.S. is postdoctoral researcher of the Research Foundation Flanders (FWO-Vlaanderen), C.L. was funded by EBMT, N.H. and B.G. were funded by Leukaemia & Lymphoma Research and S.B. by Cancer Research U.K. This work was supported in part by research grants of the FWO-Vlaanderen (G.0082.08), the Belgian Foundation against Cancer, and the Methusalem program of the Flemish Government.

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  1. Laboratory of Experimental Haematology, Vaccine and Infectious Disease Institute, Antwerp University Hospital, University of Antwerp, Wilrijkstraat 10, 2650, Antwerp, Belgium

    Evelien L. J. Smits & Viggo F. I. Van Tendeloo

  2. Department of Haematology, Southampton University Hospital Trust, Southampton, SO16 6YD, UK

    Cindy Lee & Kim Orchard

  3. Cancer Sciences Division (MP824), University of Southampton, Somers Cancer Research Building, Southampton, SO16 6YD, UK

    Cindy Lee, Suzanne Brooks & Barbara-ann Guinn

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

    Nicola Hardwick & Barbara-ann Guinn

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  1. Evelien L. J. Smits
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Correspondence to Evelien L. J. Smits.

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Smits, E.L.J., Lee, C., Hardwick, N. et al. Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia. Cancer Immunol Immunother 60, 757–769 (2011). https://doi.org/10.1007/s00262-011-1022-6

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