In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines Journal Article
| Authors: | Nishikawa, H.; Sato, E.; Briones, G.; Chen, L. M.; Matsuo, M.; Nagata, Y.; Ritter, G.; Jager, E.; Nomura, H.; Kondo, S.; Tawara, I.; Kato, T.; Shiku, H.; Old, L. J.; Galán, J. E.; Gnjatic, S. |
| Article Title: | In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines |
| 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. |
| Keywords: | immunohistochemistry; controlled study; human cell; nonhuman; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; animal tissue; melanoma; animal experiment; animal model; membrane proteins; in vivo study; tumor regression; cell line, tumor; mice, inbred balb c; antigen presentation; antigens, neoplasm; cancer vaccine; drug mechanism; cancer vaccines; ny eso 1 antigen; major histocompatibility antigen class 2; cd4+ t lymphocyte; cd4-positive t-lymphocytes; recombinant proteins; protein secretion; tumor; enzyme linked immunospot assay; antibodies, neoplasm; drug delivery system; major histocompatibility antigen class 1; peripheral lymphocyte; epitopes; salmonella typhimurium |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 116 |
| Issue: | 7 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2006-07-03 |
| Start Page: | 1946 |
| End Page: | 1954 |
| Language: | English |
| DOI: | 10.1172/jci28045 |
| PUBMED: | 16794737 |
| PROVIDER: | scopus |
| PMCID: | PMC1481660 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 56" - "Export Date: 4 June 2012" - "CODEN: JCINA" - "Source: Scopus" |
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