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Electrochemotherapy and inducible T cell co-stimulator (iCOS) antibody therapy: a novel combinational therapy for the enhanced treatment in cancers of poor prognosis

  • Morgan O'Brien1,
  • Patrick Forde1,
  • Derek Power2 and
  • Declan Soden1
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P116

https://doi.org/10.1186/2051-1426-2-S3-P116

Published: 6 November 2014

Keywords

Germinal CenterHumoral Immune ResponseTumour Associate AntigenTreated TumourChemotherapy Drug

The correlation between the level of immune involvement and immune cell infiltration within a treated tumour and the clinical outcome for patients has been well established in many solid tumour types. High numbers of tumour infiltrating lymphocytes has been associated with a significantly improved prognosis. Some of the key cell types involved are CD3 + and CD8 + T cells, B cells and APCs such as dendritic cells (DCs).

Cork Cancer Research Centre (CCRC) has long utilised an ablative cancer treatment that involves delivering a pulse of electrical energy (electroporation) directly to the tumour. This treatment results in the formation of reversible pores in the cell membrane, allowing up to a 1000 fold increase in chemotherapy drug absorption (Electrochemotherapy). A significant benefit of this non thermal ablation is the release of tumour associated antigens into the microenvironment, leading to activation of APCs and subsequent cross presentation of the antigens to circulating T and B cells. While ECT facilitates the priming of a favourable immune response, the combination of iCOS antibody, capable of stimulating T cell proliferation, causes a very robust mediated regression of treated tumours. In addition, ICOS is involved in humoral immune responses (B cell germinal center formation) and increases the production of IL-4.

Preclinical work in aggressive murine models has yielded very encouraging results. The combinational therapy has achieved cures in both colorectal (CT26) and metastatic lung (LLC) cancer cell lines. Follow up immunohistochemical staining confirmed the presence of tumour infiltrating CD3+ and CD8+ T cells, CD45R+ B cells and CD11c+ DCs, post treatment.

Authors’ Affiliations

(1)
Cork Cancer Research Centre, Cork City, Ireland
(2)
Cork University Hopital, Cork City, Ireland

Copyright

© Brien et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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