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Immunotherapy of myeloid leukaemia

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Abstract

The treatment of myeloid leukaemia has progressed in recent years with the advent of donor leukocyte infusions (DLI), haemopoietic stem cell transplants (HSCTs) and targeted therapies. However, relapse has a high associated morbidity rate and a method for removing diseased cells in first remission, when a minimal residual disease state is achieved and tumour load is low, has the potential to extend remission times and prevent relapse especially when used in combination with conventional treatments. Acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are heterogeneous diseases which lack one common molecular target while chronic myeloid leukaemia (CML) patients have experienced prolonged remissions through the use of targeted therapies which remove BCR-ABL+ cells effectively in early chronic phase. However, escape mutants have arisen and this therapy has little effectivity in the late chronic phase. Here we review the immune therapies which are close to or in clinical trials for the myeloid leukaemias and describe their potential advantages and disadvantages.

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Abbreviations

Ab:

antibody

AML:

acute myeloid leukaemia

APC:

antigen presenting cells

APL:

acute promyelocytic leukaemia

ATRA:

all trans-retinoic acid

CML:

chronic myeloid leukaemia

CT:

cancer-testis

CTL:

cytotoxic T-lymphocyte

DC:

dendritic cell

DLI:

donor leukocyte infusion

FLT3:

FMS-like tyrosine kinase 3

GvL:

graft versus leukaemia

HSCT:

haemopoietic stem cell transplant

LAA:

leukaemia associated antigen

MDS:

myelodysplastic syndrome

NK:

natural killer

OFA-iLRP:

Oncofetal antigen-immature laminin receptor

pMHC:

peptide-MHC

PRAME:

preferentially expressed antigen of melanoma

RHAMM:

receptor for hyaluronic acid-mediated motility

RIC:

reduced intensity conditioning

SEREX:

serological analysis of recombinant cDNA expression libraries

SNPs:

single nucleotide polymorphisms

TCR:

T cell receptor

TRAIL:

tumour necrosis factor α-related apoptosis-inducing ligand

WT-1:

Wilm’s Tumour-1

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Acknowledgments

We would like to thank Dr. Nigel Westwood, Dr. Shahram Kordasti and Dr. Wendy Ingram for their critical review of the manuscript. B.G. is funded by the Leukaemia Research Fund.

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

    Barbara-Ann Guinn, Azim Mohamedali & N. Shaun B. Thomas

  2. Department of Haematology, School of Medicine, University of Cardiff, Cardiff, CF4 4XN, UK

    Ken I. Mills

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  1. Barbara-Ann Guinn
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Correspondence to Barbara-Ann Guinn.

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Guinn, BA., Mohamedali, A., Thomas, N.S.B. et al. Immunotherapy of myeloid leukaemia. Cancer Immunol Immunother 56, 943–957 (2007). https://doi.org/10.1007/s00262-006-0267-y

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