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

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Abstract
Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimuriumvaccine 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 ofcancer 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. typhimuriumtype III secretion system is a promising novel strategy for cancer vaccine development.