In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines.
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.
Nishikawa
Hiroyoshi
H
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.
Sato
Eiichi
E
Briones
Gabriel
G
Chen
Li-Mei
LM
Matsuo
Mitsutoshi
M
Nagata
Yasuhiro
Y
Ritter
Gerd
G
Jäger
Elke
E
Nomura
Hideki
H
Kondo
Shigeto
S
Tawara
Isao
I
Kato
Takuma
T
Shiku
Hiroshi
H
Old
Lloyd J
LJ
Galán
Jorge E
JE
Gnjatic
Sacha
S
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D000939:Epitopes; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D008565:Membrane Proteins; D011994:Recombinant Proteins