CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Antitumor activity of a Salmonella Typhi vaccine strain in a mouse model of T-cell lymphoma
Autor/es:
VENDRELL, A.; TESONE, A.; DE TORO, J.; HERSCHLIK, L.; GRAVISACO, M.J.; GOIN J.C.; LAROTONDA, G.; MONGINI, C.; WALDNER, C.
Lugar:
Milan
Reunión:
Congreso; 15th International Congress of Immunology; 2013
Institución organizadora:
International Union of Immunological Societies (IUIS)
Resumen:
Previously we demonstrated the therapeutic efficacy of an attenuated vaccine strain of SalmonellaTyphi as a cancer immunotherapy in a mouse model of subcutaneous T cell lymphoma. EL4 tumor-bearing mice treated with Salmonella Typhi CVD 915, by injection into the tumor and in the area of the draining lymph nodes, showed reduced tumor growth and increased survival. In this work, we further studied the therapeutic efficacy and the antitumor effector mechanisms promoted by this bacterium. Our results indicate that the treatment with Salmonella promoted a reduction in the mitotic index of the tumors (p <0.05) and delayed the development of palpable metastases in the lymph nodes (p <0.001). Furthermore, the administration of Salmonella in tumor-bearing mice promoted leukocyte infiltration, mainly neutrophils (p <0.01) and decreased IL- 10 levels in the tumor microenvironment (p <0.05), and also reduced LTreg frequency in tumor draining lymph nodes. Under these conditions, Salmonella remained viable within the tumor, and tumor- infiltrating neutrophils released TNF-alpha and expressed bacterial antigens. Finally, Salmonella was found to bind to tumor cells and exert oncolytic activity upon direct contact with the tumor cell. These results demonstrate the efficacy of a vaccine strain of Salmonella Typhi as an oncolytic and immunotherapeutic agent against a highly malignant tumor