Cancer Immunology, Immunotherapy

, Volume 55, Issue 11, pp 1443–1450

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

  • M. Tangney
  • G. Casey
  • J. O. Larkin
  • C. G. Collins
  • D. Soden
  • J. Cashman
  • M. C. Whelan
  • G. C. O’Sullivan
Symposium Paper

DOI: 10.1007/s00262-006-0169-z

Cite this article as:
Tangney, M., Casey, G., Larkin, J.O. et al. Cancer Immunol Immunother (2006) 55: 1443. doi:10.1007/s00262-006-0169-z

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.

Keywords

ImmunotherapyNon-viralGene therapyElectroporationGM-CSFB7-1

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

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • M. Tangney
    • 1
    • 2
  • G. Casey
    • 1
  • J. O. Larkin
    • 1
  • C. G. Collins
    • 1
  • D. Soden
    • 1
  • J. Cashman
    • 1
  • M. C. Whelan
    • 1
  • G. C. O’Sullivan
    • 1
  1. 1.Cork Cancer Research Centre, Mercy University Hospital and Leslie C. Quick Jnr. LaboratoryUniversity College CorkCorkIreland
  2. 2.Cork Cancer Research, Mercy University HospitalNational University of IrelandCorkIreland