Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.
AffiliationCork Cancer Research Centre, Mercy University Hospital and Leslie C Quick Jnr, Laboratory, University College Cork, Cork, Ireland.
Cell Line, Tumor
Combined Modality Therapy
Granulocyte-Macrophage Colony-Stimulating Factor/genetics
Interleukin-2 Receptor alpha Subunit/immunology
Mice, Inbred BALB C
MetadataShow full item record
CitationCancer Gene Ther. 2010 Jul;17(7):501-11. Epub 2010 Feb 26.
JournalCancer gene therapy
AbstractObstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.
- Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors.
- Authors: Collins CG, Tangney M, Larkin JO, Casey G, Whelan MC, Cashman J, Murphy J, Soden D, Vejda S, McKenna S, Kiely B, Collins JK, Barrett J, Aarons S, O'Sullivan GC
- Issue date: 2006 Dec
- Immune gene therapy as a neoadjuvant to surgical excision to control metastatic cancers.
- Authors: Cashman JP, Larkin JO, Casey G, Whelan MC, Collins C, Aarons S, Tangney M, O'Sullivan GC
- Issue date: 2008 Apr 8
- Combination of CTL-associated antigen-4 blockade and depletion of CD25 regulatory T cells enhance tumour immunity of dendritic cell-based vaccine in a mouse model of colon cancer.
- Authors: Saha A, Chatterjee SK
- Issue date: 2010 Feb
- Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease.
- Authors: Tangney M, Casey G, Larkin JO, Collins CG, Soden D, Cashman J, Whelan MC, O'Sullivan GC
- Issue date: 2006 Nov
- Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy.
- Authors: Li B, Lalani AS, Harding TC, Luan B, Koprivnikar K, Huan Tu G, Prell R, VanRoey MJ, Simmons AD, Jooss K
- Issue date: 2006 Nov 15