Immunotherapy for the liver metastases prevention with a vaccine strain of an attenuated Salmonella Typhi

ALEJANDRINA VENDRELL; AGUSTINA TESONE; DE TORO JULIETA; HERSCHLIK LETICIA; GRAVISACO MARIA JOSE; GOIN, JUAN C; GERARDO LAROTONDA; MONGINI CLAUDIA; WALDNER CLAUDIA

Milán

Congreso; 15th International congress of immunology; 2013

IUIS

In previous studies we demonstrated that an attenuated Salmonella Typhi vaccine strain (CVD 915) induces tumor-specific immune and therapeutic responses, following intratumoral and subcutaneous inoculations, in mice bearing a subcutaneous mammary adenocarcinoma (LM3). The aim of this work was to study whether orogastric (og) administration of CVD 915 can prevent tumor cell implantation in liver, in a mouse model of liver metastases. Each BALB/c mouse received og 5x109UFC of CVD 915 or PBS (control group). After 24 hours, mice were subjected to surgery and 50,000 LM3 cells were injected into their spleens. Then, a splenectomy was performed. After 24 h of bacterial treatment, CVD 915-treated mice exhibited elevated IFN-γ serum levels. Seven days later, Salmonella treatment stimulated the proinflammatory Th1 cytokines production (enhanced IFN-γ level in serum, p<0.001, and detectable serum TNF-α and IL-12 levels). The prophylactic treatment with Salmonella significantly decreased the occurrence of liver metastases as well as their average volume (1.9 vs. 6.2 mm3) 21 days after surgery, as compared with control mice (p<0.05). Moreover, at that time, an increased frequency of CD4+ lymphocytes but a decreased proportion of B cells (B220+) in both liver and peripheral blood were observed in CVD 915-treated animals (p<0.05). These results indicate that a CVD 915-based immunotherapy used preventively via og route induces an antitumor immunity and prevents the implantation of metastasis in a vital organ. The use of this vaccine as an adjunct therapy to conventional cancer treatments, such as surgery, should be assessed in the future.