Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

Hdl Handle:
http://hdl.handle.net/10147/206384
Title:
Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.
Authors:
Whelan, M C; Casey, G; MacConmara, M; Lederer, J A; Soden, D; Collins, J K; Tangney, M; O'Sullivan, G C
Affiliation:
Cork Cancer Research Centre, Mercy University Hospital and Leslie C Quick Jnr, Laboratory, University College Cork, Cork, Ireland.
Citation:
Cancer Gene Ther. 2010 Jul;17(7):501-11. Epub 2010 Feb 26.
Journal:
Cancer gene therapy
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206384
DOI:
10.1038/cgt.2010.8
PubMed ID:
20186173
Abstract:
Obstacles 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.
Language:
eng
MeSH:
Animals; Antigen Presentation; Antigens, CD80/genetics; Cell Line, Tumor; Combined Modality Therapy; Fibrosarcoma/genetics/immunology/*therapy; Gene Therapy/*methods; Granulocyte-Macrophage Colony-Stimulating Factor/genetics; Humans; Immunogenetic Phenomena; Immunotherapy/*methods; Interleukin-2 Receptor alpha Subunit/immunology; Mice; Mice, Inbred BALB C; Neoplasms/genetics/immunology/*therapy; T-Lymphocytes, Regulatory/*immunology
ISSN:
1476-5500 (Electronic); 0929-1903 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorWhelan, M Cen_GB
dc.contributor.authorCasey, Gen_GB
dc.contributor.authorMacConmara, Men_GB
dc.contributor.authorLederer, J Aen_GB
dc.contributor.authorSoden, Den_GB
dc.contributor.authorCollins, J Ken_GB
dc.contributor.authorTangney, Men_GB
dc.contributor.authorO'Sullivan, G Cen_GB
dc.date.accessioned2012-01-31T16:38:28Z-
dc.date.available2012-01-31T16:38:28Z-
dc.date.issued2012-01-31T16:38:28Z-
dc.identifier.citationCancer Gene Ther. 2010 Jul;17(7):501-11. Epub 2010 Feb 26.en_GB
dc.identifier.issn1476-5500 (Electronic)en_GB
dc.identifier.issn0929-1903 (Linking)en_GB
dc.identifier.pmid20186173en_GB
dc.identifier.doi10.1038/cgt.2010.8en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206384-
dc.description.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.en_GB
dc.language.isoengen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAntigen Presentationen_GB
dc.subject.meshAntigens, CD80/geneticsen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCombined Modality Therapyen_GB
dc.subject.meshFibrosarcoma/genetics/immunology/*therapyen_GB
dc.subject.meshGene Therapy/*methodsen_GB
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor/geneticsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunogenetic Phenomenaen_GB
dc.subject.meshImmunotherapy/*methodsen_GB
dc.subject.meshInterleukin-2 Receptor alpha Subunit/immunologyen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred BALB Cen_GB
dc.subject.meshNeoplasms/genetics/immunology/*therapyen_GB
dc.subject.meshT-Lymphocytes, Regulatory/*immunologyen_GB
dc.titleEffective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.en_GB
dc.contributor.departmentCork Cancer Research Centre, Mercy University Hospital and Leslie C Quick Jnr, Laboratory, University College Cork, Cork, Ireland.en_GB
dc.identifier.journalCancer gene therapyen_GB
dc.description.provinceMunster-

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