Therapeutic effects of Salmonella typhi in a mouse model of T-cell lymphoma

• Published in: Journal of immunotherapy (1997) Vol. 36; no. 3; pp. 171 - 180
• Main Authors: Vendrell, Alejandrina, Gravisaco, María J, Goin, Juan C, Pasetti, Marcela F, Herschllik, Leticia, De Toro, Julieta, Rodríguez, Carla, Larotonda, Gerardo, Mongini, Claudia, Waldner, Claudia I
• Format: Journal Article
• Language: English
• Published: United States 01-04-2013
• Subjects: Animal models; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Female; Immunotherapy - methods; Interleukin-10 - biosynthesis; Lymph Nodes - immunology; Lymphatic Metastasis - prevention & control; Lymphoma, T-Cell - immunology; Lymphoma, T-Cell - microbiology; Lymphoma, T-Cell - therapy; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Mitotic Index; Salmonella enterica; Salmonella typhi - immunology; Typhoid-Paratyphoid Vaccines - immunology; Typhoid-Paratyphoid Vaccines - therapeutic use; Vaccines, Attenuated - therapeutic use
• DOI: 10.1097/CJI.0b013e3182886d95
• EISSN: 1537-4513
• ISSN: 1524-9557

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.