Liver and Circulating NK1.1+CD3− Cells Are Increased in Infection with Attenuated Salmonella typhimurium and Are Associated with Reduced Tumor in Murine Liver Cancer

Attenuated Salmonella typhimurium with IL-2 Gene Reduces Pulmonary Metastases in Murine Osteosarcoma

“…Individual drugs have been ineffective in treating pulmonary metastases [31], and combined therapy has not substantially altered the course of disease in patients who present with detectable pulmonary osteosarcoma metastases, as the 5-year survival rate continues to hover around 30% [9,11,37]. Our previous research demonstrates an antitumor effect in a variety of animal cancer models associated with oral dosing of attenuated Salmonella typhimurium with and without a truncated gene for human IL-2 [1,7,8,27,29,33]. This project represents the early assessment of S. typhimurium in an osteosarcoma pulmonary metastatic model.…”

“…In these studies, NK cell populations appear largely responsible for the decrease in tumor burden in salmonella-treated animals [7,8,27,29,33]. We sought to determine whether previous antitumor mechanisms of SalpIL2 could be applied to an experimental model of metastatic osteosarcoma.…”

“…Other experimental metastasis models utilizing SalpIL2 demonstrate NK expansion and involvement [7,8,27,29,33], implicating NK cell receptor involvement in the antitumor mechanism. Future studies within this model are focusing on the prophylactic use of SalpIL2 in metastatic osteosarcoma, local tumor/NK cell interaction, and the systemic cytokine response to tumor and SalpIL2.…”

“…We recently demonstrated a single oral dose of an attenuated Salmonella typhimurium genetically engineered with a gene for a truncated human interleukin-2 (SalpIL2) substantially reduces unresectable adenocarcinoma metastases to the liver in experimental treatment and prophylactic mouse models [7,8,27,29,33]. In addition, SalpIL2 reduces the volume and mass of retroperitoneal neuroblastoma tumors in an experimental murine treatment model [1].…”

Cyclooxygenase-2 Inhibition Augments the Hepatic Antitumor Effect of Oral Salmonella Typhimurium in a Model of Mouse Metastatic Colon Cancer

“…CONCLUSION U sing mice with experimental liver cancer, we have previously reported that oral inoculation with an attenuated S. typhimurium (4550) results in no morbidity, is associated with increased hepatic natural killer lymphocytes (NK1.1 ϩ CD4 Ϫ ), and is associated with reduced hepatic tumor burden. 1 Because attenuated S. typhimurium may be suited for use as an adjuvant oral antitumor therapy, we searched for a safe oral agent that may act synergistically with salmonella to reduce tumor burden, and we hypothesized that cyclooxygenase-2 (COX2) inhibition may potentiate the antitumor efficacy of orally administered S. typhimurium.…”