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Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease

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Abstract

Many patients with various types of cancers have already by the time of presentation, micrometastases in their tissues and are left after treatment in a minimal residual disease state [Am J Gastroenterol 95(12), 2000]. To prevent tumour recurrence these patients require a systemic based therapy, but current modalities are limited by toxicity or lack of efficacy. We have previously reported that immune reactivity to the primary tumour is an important regulator of micrometastases and determinant of prognosis. This suggests that recruitment of specific anti-tumour mechanisms within the primary tumour could be used advantageously for tumour control as either primary or neo-adjuvant treatments. Recently, we have focused on methods of stimulating immune eradication of solid tumours and minimal residual disease using gene therapy approaches. Gene therapy is now a realistic prospect and a number of delivery approaches have been explored, including the use of viral and non-viral vectors. Non-viral vectors have received significant attention since, in spite of their relative delivery inefficiency, they may be safer and have greater potential for delivery of larger genetic units. By in vivo electroporation of the primary tumour with plasmid expressing GM-CSF and B7-1, we aim to stimulate immune eradication of the treated tumour and associated metastases. In this symposium report, we describe an effective gene based approach for cancer immunotherapy by inducing cytokine and immune co-stimulatory molecule expression by the growing cells of the primary tumour using a plasmid electroporation gene delivery strategy. We discuss the potential for enhancement of this therapy by its application as a neoadjuvant to surgical excision and by its use in combination with suppressor T cell depletion.

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Abbreviations

APC:

Antigen presenting cell

CTL:

Cytotoxic T lymphocytes

DC:

Dendritic cell

EP:

Electroporation

GM-CSF:

Granulocyte macrophage-colony

LAK:

Lymphokine activated killer cell

SF:

Stimulating factor

i.v.:

Intravenous

MRD:

Minimal residual disease

s.c.:

Subcutaneous

TAA:

Tumour associated antigen

TIL:

Tumour infiltrating lymphocyte

Treg:

Regulatory T cell

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Acknowlegment

Mark Tangney and Gerald C. O’Sullivan are funded by the Health Research Board of Ireland.

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Authors and Affiliations

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

    M. Tangney, G. Casey, J. O. Larkin, C. G. Collins, D. Soden, J. Cashman, M. C. Whelan & G. C. O’Sullivan

  2. Cork Cancer Research, Mercy University Hospital, National University of Ireland, Cork, Ireland

    M. Tangney

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  1. M. Tangney
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  2. G. Casey
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Corresponding author

Correspondence to M. Tangney.

Additional information

This article is a symposium paper from the Annual Meeting of the “International Society for Cell and Gene Therapy of Cancer”, held in Shenzhen, China, on 9–11 December 2005.

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Tangney, M., Casey, G., Larkin, J.O. et al. Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease. Cancer Immunol Immunother 55, 1443–1450 (2006). https://doi.org/10.1007/s00262-006-0169-z

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  • DOI: https://doi.org/10.1007/s00262-006-0169-z

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