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Salmonella typhimurium stimulation combined with tumour-derived heat shock proteins induces potent dendritic cell anti-tumour responses in a murine model.
Shilling, D A; Smith, M J; Tyther, R; Sheehan, D; England, K; Kavanagh, E G; Redmond, H P; Shanahan, F; O'Mahony, L.
Affiliation
  • Shilling DA; Alimentary Pharmabiotic Centre, National University of Ireland, Cork, Ireland.
Clin Exp Immunol ; 149(1): 109-16, 2007 Jul.
Article in En | MEDLINE | ID: mdl-17459080
Appropriate activation of the immune system and effective targeting of tumour cells are the primary hurdles to be overcome for cancer immunotherapy to be successful and applicable to a wide range of tumour types. Our studies have examined the ability of bacterial-stimulated dendritic cells (DCs), loaded with tumour-associated antigens, to inhibit tumour growth in a murine model. Immature murine bone marrow-derived DCs were stimulated in vitro with the cytoplasmic fraction (CM) of Salmonella typhimurium in combination with heat shock proteins (hsps) from 4T1 tumours, isolated using heparin affinity chromatography. Activated DCs were administered subcutaneously. Tumours were generated by orthotopic inoculation of 4T1 cells in Balb/c mice. Primary tumour growth was measured using Vernier calipers, while lung metastases were measured using the clonogenic assay. S. typhimurium CM induced potent tumour necrosis factor (TNF)-alpha responses from DCs accompanied by significant up-regulation of CD80 and CD86 expression. When injected into mice, bacterial-stimulated DCs loaded with 4T1 hsps inhibited the formation of new 4T1 tumours and reduced the growth rate of established tumours. In addition, the number of lung metastatic nodules was reduced significantly in the DC-treated mice (1.6 +/- 0.6 versus 245.9 +/- 55.6, P = 0.0015). DCs stimulated with CM alone, exposed to tumour hsps alone or exposed to tumour hsps from an unrelated tumour cell line did not induce a protective immune response. Dendritic cells primed with a proinflammatory bacterial stimulus and tumour-associated antigens induce a protective anti-tumour immune response in this murine model.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Salmonella typhimurium / Dendritic Cells / Cancer Vaccines / Heat-Shock Proteins / Mammary Neoplasms, Experimental Type of study: Prognostic_studies Limits: Animals Language: En Journal: Clin Exp Immunol Year: 2007 Document type: Article Affiliation country: Irlanda Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Salmonella typhimurium / Dendritic Cells / Cancer Vaccines / Heat-Shock Proteins / Mammary Neoplasms, Experimental Type of study: Prognostic_studies Limits: Animals Language: En Journal: Clin Exp Immunol Year: 2007 Document type: Article Affiliation country: Irlanda Country of publication: Reino Unido