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Analogue peptides for the immunotherapy of human acute myeloid leukemia

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies.

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Abbreviations

AML:

Acute myeloid leukemia

CEA:

Carcinoembryonic antigen

CML:

Chronic myeloid leukemia

CTA:

Cancer–testis antigen

CTL:

Cytotoxic T lymphocyte

HLA:

Human leukocyte antigen

IFA:

Incomplete Freund’s adjuvant

LAA:

Leukemia associated antigen

LSC:

Leukemic stem cell

MAGE:

Melanoma associated antigen

MRD:

Minimal residual disease

NPM1mut :

Nucleophosmin 1 gene mutation

PASD1:

Per Arnt Sim Domain containing 1

pMHC:

Peptide-major histocompatibility complex

SEREX:

Serological analysis of expression cDNA libraries

TCR:

T-cell receptor

Wt:

Wild type

WT1:

Wilms’ tumor gene product 1

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Acknowledgments

We would like to thank Dr Sarah Buchan for her helpful insights. Dr Susanne Hofmann received funding from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and Drs Nicola Hardwick and Barbara Guinn from Leukaemia and Lymphoma Research.

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Author notes

  1. Andrew Mead, Aleksandrs Malinovskis & Barbara-ann Guinn

    Present address: Department of Life Sciences, University of Bedfordshire, Park Square, Luton, LU1 3JU, UK

  2. Nicola R. Hardwick

    Present address: Division of Translational Vaccine Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA

Authors and Affiliations

  1. Third Clinic for Internal Medicine, University of Ulm, Ulm, Germany

    Susanne Hofmann

  2. Department of Haematological Medicine, Guy’s, King’s & St. Thomas’ School of Medicine, The Rayne Institute, King’s College London, 123 Coldharbour Lane, London, UK

    Nicola R. Hardwick & Barbara-ann Guinn

  3. Cancer Sciences Unit, Southampton University Hospitals Trust, University of Southampton, Southampton, UK

    Barbara-ann Guinn

Authors
  1. Susanne Hofmann
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  2. Andrew Mead
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  3. Aleksandrs Malinovskis
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  4. Nicola R. Hardwick
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  5. Barbara-ann Guinn
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Corresponding author

Correspondence to Barbara-ann Guinn.

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The authors declare there are no competing financial interests in relation to the work described.

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Hofmann, S., Mead, A., Malinovskis, A. et al. Analogue peptides for the immunotherapy of human acute myeloid leukemia. Cancer Immunol Immunother 64, 1357–1367 (2015). https://doi.org/10.1007/s00262-015-1762-9

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  • DOI: https://doi.org/10.1007/s00262-015-1762-9

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