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New targets for the immunotherapy of colon cancer—does reactive disease hold the answer?

Cancer Gene Therapy volume 20, pages 157–168 (2013)Cite this article

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Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women, posing a serious demographic and economic burden worldwide. In the United Kingdom, CRC affects 1 in every 20 people and it is often detected once well established and after it has spread beyond the bowel (Stage IIA–C and Stage IIIA–C). A diagnosis at such advanced stages is associated with poor treatment response and survival. However, studies have identified two sub-groups of post-treatment CRC patients—those with good outcome (reactive disease) and those with poor outcome (non-reactive disease). We aim to review the state-of-the-art for CRC with respect to the expression of cancer-testis antigens (CTAs) and their identification, evaluation and correlation with disease progression, treatment response and survival. We will also discuss the relationship between CTA expression and regulatory T-cell (Treg) activity to tumorigenesis and tumor immune evasion in CRC and how this could account for the clinical presentation of CRC. Understanding the molecular basis of reactive CRC may help us identify more potent novel immunotherapeutic targets to aid the effective treatment of this disease. In this review, based on our presentation at the 2012 International Society for the Cell and Gene Therapy of Cancer annual meeting, we will summarize some of the most current advances in CTA and CRC research and their influence on the development of novel immunotherapeutic approaches for this common and at times difficult to treat disease.

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Abbreviations

AJCC:

American Joint Committee on Cancer

AML:

acute myeloid leukemia

CEA:

carcinoembryonic antigen

CRC:

colorectal cancer

CTA:

cancer-testis antigen

CTL:

cytotoxic T lymphocyte

DAC:

5-aza-2′-deoxycytidine

DC:

dendritic cells

EBV:

Epstein–Barr virus

GIST:

gastrointestinal stromal tumor

IDP:

intrinsically disordered protein

pMHC:

peptide MHC

RAYS:

recombinant antigen expression on yeast surface

SADA:

serum antibody detection array

SEREX:

serological identification of antigens by recombinant expression cloning

SERPA:

serological proteome analysis

SSX:

synovial sarcoma X antigen

SSX2:

synovial sarcoma X breakpoint-2

TAA:

tumor-associated antigen

TNM:

tumor nodes metastases

Tregs:

regulatory T cells; TSP50: testes-specific protease 50

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Acknowledgements

This work was funded in part by Cork Cancer Research Center. SAB and SEB were funded by Cancer Research UK.

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Authors and Affiliations

  1. Department of Life Sciences, University of Bedfordshire, Park Square, Luton, UK

    V Boncheva & B-A Guinn

  2. Cancer Sciences Unit, Somers Cancer Sciences Building, Southampton University Hospitals, University of Southampton, Southampton, UK

    S A Bonney, S E Brooks, A Mirnezami & B-A Guinn

  3. Cork Cancer Research Centre, Mercy University Hospital and Leslie C. Quick Jnr. Laboratory, University College Cork, Cork, Ireland

    M Tangney & G O'Sullivan

  4. Department of Haematological Medicine, King’s College London School of Medicine, London, UK

    B-A Guinn

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  1. V Boncheva
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Boncheva, V., Bonney, S., Brooks, S. et al. New targets for the immunotherapy of colon cancer—does reactive disease hold the answer?. Cancer Gene Ther 20, 157–168 (2013). https://doi.org/10.1038/cgt.2013.5

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