Therapeutic efficacy of tumor-targetingSalmonella typhimuriumA1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models

Abstract

Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis.

Bacterial cancer therapy in autochthonous colorectal cancer affects tumor growth and metabolic landscape

“…The advancement of molecular genetics has enabled bacteria to be effectively attenuated to remove adverse side-effects and engineered to deliver different payloads. Hence, there has been a resurgence in interest in BCT in the past 20 years, with many studies showing efficacy of attenuated bacterial treatments in xenograft and orthotopic transplant tumor models, with Salmonella enterica serovar Typhimurium (STm) being by far the most studied (3)(4)(5)(6)(7)(8)(9). Attenuated STm are extremely tumor-tropic: a therapy that can give such tumor tissue selectivity is very desirable and enables further engineering to deliver drugs, immune adjuvants or other anti-tumor agents (3).…”

Adjuvant treatment with tumor-targetingSalmonella typhimuriumA1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model

“…In a recent study, we found that Salmonella typhimurium A1-R was active as monotherapy on liver metastasis in the orthotopic HT-29 mouse model. The results of that study demonstrated the potential of S. typhimurium A1-R targeting of liver metastasis [ 44 ].…”

Angiogenic inhibitors delivered by the type III secretion system of tumor-targeting Salmonella typhimurium safely shrink tumors in mice

“…As has been proven by several laboratories, Salmonella alone could induce modest antitumor effects in animal models although the mechanisms responsible for this are not yet fully understood (Hiroshima et al 2013 ; Murakami et al 2015 ). The combination of bacteria with angiogenic inhibitors may elicit a strong synergistic effect and directly contribute to tumor destruction through the release of nitric oxide (Griffon et al 1998 ), protease (Le Negrate et al 2008 ), pore-forming agents (Shi et al 2016 ) and therapeutic factors.…”