title: Therapeutic effects of Salmonella typhi in a mouse model of T-cell lymphoma.
abstract: In this study, we assessed the effectiveness of a live, attenuated Salmonella enterica serovar Typhi (S. Typhi) vaccine strain as a cancer immunotherapy in a mouse model of metastatic T-cell lymphoma. EL4 tumor-bearing C57BL/6J mice immunized with S. Typhi strain CVD 915, by injection into the tumor and the draining lymph node areas, displayed a significant decrease in tumor growth, a reduction in the mitotic index (MI) of tumors, a delayed development of palpable lymph node metastases and most importantly improved survival, compared to untreated mice. Besides, complete tumor regression was achieved in a small number of bacteria-treated mice. A successful therapeutic response associated with a significant reduction of tumor mass was evident as early as 5 days after treatment. The administration of Salmonella to tumor-bearing mice promoted early cellular infiltration (mainly neutrophils) within the tumor, and was accompanied by a decreased intratumoral interleukin 10 production as well as by leukocyte expansion in tumor draining lymph nodes. A tumor-specific memory immune response was induced in most of cured animals, as evidenced by the lack of tumor growth after a rechallenge with the same tumor. EL4 cells cultured with live Salmonella failed to proliferate and underwent apoptosis in a dose-dependent, time-dependent, and contact-dependent manner. To our knowledge, these results demonstrate for the first time the efficacy of a S. Typhi vaccine strain as an oncolytic and immunotherapeutic agent against a highly malignant tumor and support the use of S. Typhi-based vaccine strains in cancer therapy.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos-Consejo Nacional de Investigaciones Científicas y Técnicas (CEFyBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Alejandrina
authors.initials: A
authors.lastname: Vendrell
authors.forename: María J
authors.initials: MJ
authors.lastname: Gravisaco
authors.forename: Juan C
authors.initials: JC
authors.lastname: Goin
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Leticia
authors.initials: L
authors.lastname: Herschllik
authors.forename: Julieta
authors.initials: J
authors.lastname: De Toro
authors.forename: Carla
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Gerardo
authors.initials: G
authors.lastname: Larotonda
authors.forename: Claudia
authors.initials: C
authors.lastname: Mongini
authors.forename: Claudia I
authors.initials: CI
authors.lastname: Waldner
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008207:Lymphatic Metastasis / Q000517:prevention & control; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008940:Mitotic Index; D012485:Salmonella typhi / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014613:Vaccines, Attenuated / Q000627:therapeutic use
chemical_list: D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D016753:Interleukin-10