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

Abstract

Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.

Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model

“…Since DOX is presently considered first-line therapy of soft tissue sarcoma, the combination of DOX with S. typhimurium A1-R has important future clinical potential, which we hope can be realized in the near future. Another potential future clinical strategy is to combine sarcoma surgery with adjuvant S. typhimurium A1-R which we have shown to be highly effective in mouse models [ 35 ].…”

High-efficacy targeting of colon-cancer liver metastasis withSalmonella typhimuriumA1-R via intra-portal-vein injection in orthotopic nude-mouse models

“…HT29 human colon cancer cells expressing RFP [ 34 , 47 – 49 ] were maintained in RPMI 1640 medium (Invitrogen, Carlsbad, CA, USA) supplemented with heat-inactivated 10% fetal bovine serum (FBS) (Gemini Biologic Products, Calabasas, CA), 2 mM glutamine, 100 units/ml penicillin, 100 μg/ml streptomycin and 0.25 μg/ml amphotericin B (Life Technologies, Inc., Grand Island, NY). The cells were incubated at 37°C in 5% CO 2 .…”

“…The results of this previous study demonstrated the future clinical potential of S. typhimurium A1-R targeting of liver metastasis [34]. …”

“…In orthotopic mouse models, S. typhimurium A1-R, delivered iv, targeted liver metastases and significantly reduced their growth. The results of this previous study demonstrated the future clinical potential of S. typhimurium A1-R targeting of liver metastasis [ 34 ].…”

Bacteria-cancer interactions: bacteria-based cancer therapy

“…Another S . Typhimurium strain, YB1, which was derived from SL7207 by placing the essential gene asd under the control of a hypoxia-induced promoter, could not survive in normal tissue without an exogenous supply of diaminopimelic acid, although it could still colonize hypoxic tumors; thus, this strain causes reduced damage to normal tissue while retaining its tumor-targeting ability 21,47,86,87 . Furthermore, deletion of the purI and purD genes resulted in the need for exogenous adenine, which increased the ability of the bacteria to efficiently proliferate in purine-rich regions, such as tumor tissue 2,88 .…”