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

Hiroyoshi Nishikawa, Eiichi Sato, Gabriel Briones, Li Mei Chen, Mitsutoshi Matsuo, Yasuhiro Nagata, Gerd Ritter, Elke Jäger, Hideki Nomura, Shigeto Kondo, Isao Tawara, Takuma Kato, Hiroshi Shiku, Lloyd J. Old, Jorge E. Galán, Sacha Gnjatic

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

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.

Original languageEnglish
Pages (from-to)1946-1954
Number of pages9
JournalJournal of Clinical Investigation
Volume116
Issue number7
DOIs
StatePublished - 3 Jul 2006
Externally publishedYes

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