In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines |
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| Authors: | Nishikawa Hiroyoshi Sato Eiichi Briones Gabriel Chen Li-Mei Matsuo Mitsutoshi Nagata Yasuhiro Ritter Gerd Jäger Elke Nomura Hideki Kondo Shigeto Tawara Isao Kato Takuma Shiku Hiroshi Old Lloyd J Galán Jorge E Gnjatic Sacha |
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| Affiliation: | 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. |
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| 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. |
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