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J Clin Invest. 2006 Jul;116(7):1946-54. Epub 2006 Jun 22.

In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines.

Author information

1
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.

Abstract

Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimurium vaccine strain to deliver the NY-ESO-1 tumor antigen (S. typhimurium-NY-ESO-1) through a type III protein secretion system. The S. typhimurium-NY-ESO-1 construct elicited NY-ESO-1-specific CD8+ and CD4+ T cells from peripheral blood lymphocytes of cancer patients in vitro. Oral administration of S. typhimurium-NY-ESO-1 to mice resulted in the regression of established NY-ESO-1-expressing tumors. Intratumoral inoculation of S. typhimurium-NY-ESO-1 to NY-ESO-1-negative tumors resulted in delivery of antigen in vivo and led to tumor regression in the presence of preexisting NY-ESO-1-specific CD8+ T cells. Specific T cell responses against at least 2 unrelated tumor antigens not contained in the vaccine were observed, demonstrating epitope spreading. We propose that antigen delivery through the S. typhimurium type III secretion system is a promising novel strategy for cancer vaccine development.

PMID:
16794737
PMCID:
PMC1481660
DOI:
10.1172/JCI28045
[Indexed for MEDLINE]
Free PMC Article

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