Development of Oxytolerant Salmonella typhimurium Using Radiation Mutation Technology (RMT) for Cancer Therapy

Gao, Shuang; Jung, Jong‐Hyun; Lin, Shunmei; Jang, A-Yeung; Zhi, Yong; Ahn, Kyu Jeung; Ji, Hyun-Jung; Lim, Jae Hyang; Guo, Huichen; Choy, Hyon E.; Lim, Sangyong; Seo, Ho Seong

doi:10.1038/s41598-020-60396-6

Cited by 19 publications

(20 citation statements)

References 56 publications

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“…Positive results were also seen when S. typhi A1-R was used in combination with chemotherapy drugs; this concurrent treatment promoted targeting of S. typhi A1-R in melanoma PDOX (Patient-derived orthotopic xenograft) mouse models; this melanoma was previously resistant to chemotherapy treatment [ 164 ]. Studies are ongoing to investigate the use of Salmonella as an anti-tumour therapy [ 163 , 165 ]. Salmonella -based therapies have proven to specifically target and penetrate tumour tissue.…”

Section: Recent Advances In Potential Cytotoxic Gene Therapiesmentioning

confidence: 99%

The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development

et al. 2022

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Background Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes. Certain residents of the human microbiome have been identified as potentially playing a role, including: Helicobacter pylori, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Porphyromonas gingivalis. Main body In this review, we explore the current evidence that indicate a link between the human microbiome and cancer. Microbiome compositional changes have been well documented in cancer patients. Furthermore, pathogenic microbes harbouring specific virulence factors have been implicated in driving the carcinogenic activity of various malignancies including colorectal, gastric and pancreatic cancer. The associated genetic mechanisms with possible roles in cancer will be outlined. It will be indicated which microbes have a potential direct link with cancer cell proliferation, tumorigenesis and disease progression. Recent studies have also linked certain microbial cytotoxins and probiotic strains to cancer cell death, suggesting their potential to target the tumour microenvironment given that cancer cells are integral to its composition. Studies pertaining to such cytotoxic activity have suggested the benefit of microbial therapies in oncological treatment regimes. It is also apparent that bacterial pathogenic protein products encoded for by certain loci may have potential as oncogenic therapeutic targets given their possible role in tumorigenesis. Conclusion Research investigating the impact of the human microbiome in cancer has recently gathered pace. Vast amounts of evidence indicate the human microbiome as a potential player in tumorigenesis and progression. Promise in the development of cancer biomarkers and in targeted oncological therapies has also been demonstrated, although more studies are needed. Despite extensive in vitro and in vivo research, clinical studies involving large cohorts of human patients are lacking. The current literature suggests that further intensive research is necessary to validate both the role of the human microbiome in cancer, and the use of microbiome modification in cancer therapy.

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Section: Recent Advances In Potential Cytotoxic Gene Therapiesmentioning

confidence: 99%

The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development

et al. 2022

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“…A Salmonella strain (KST0650) was developed as an oxytolerant-attenuated variant from the parental strain KST0649 (∆ptsI∆crr), via the application of radiation mutation technology (RMT). This newly developed strain was shown to have a 20-times-higher replication rate in cancer cells lines (CT26) and was comparatively less virulent than the parental strain KST0649 [67].…”

Section: Pathogenic Bacteria In Bbctmentioning

confidence: 99%

Bacterial-Based Cancer Therapy (BBCT): Recent Advances, Current Challenges, and Future Prospects for Cancer Immunotherapy

et al. 2021

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Currently approximately 10 million people die each year due to cancer, and cancer is the cause of every sixth death worldwide. Tremendous efforts and progress have been made towards finding a cure for cancer. However, numerous challenges have been faced due to adverse effects of chemotherapy, radiotherapy, and alternative cancer therapies, including toxicity to non-cancerous cells, the inability of drugs to reach deep tumor tissue, and the persistent problem of increasing drug resistance in tumor cells. These challenges have increased the demand for the development of alternative approaches with greater selectivity and effectiveness against tumor cells. Cancer immunotherapy has made significant advancements towards eliminating cancer. Our understanding of cancer-directed immune responses and the mechanisms through which immune cells invade tumors have extensively helped us in the development of new therapies. Among immunotherapies, the application of bacteria and bacterial-based products has promising potential to be used as treatments that combat cancer. Bacterial targeting of tumors has been developed as a unique therapeutic option that meets the ongoing challenges of cancer treatment. In comparison with other cancer therapeutics, bacterial-based therapies have capabilities for suppressing cancer. Bacteria are known to accumulate and proliferate in the tumor microenvironment and initiate antitumor immune responses. We are currently well-informed regarding various methods by which bacteria can be manipulated by simple genetic engineering or synthetic bioengineering to induce the production of anti-cancer drugs. Further, bacterial-based cancer therapy (BBCT) can be either used as a monotherapy or in combination with other anticancer therapies for better clinical outcomes. Here, we review recent advances, current challenges, and prospects of bacteria and bacterial products in the development of BBCTs.

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“…This strain was effectively delivered to cancer cells and tumor tissues via the Salmonella type III secretion system (T3SS). In addition, combination treatment with KST0652 plus radiation showed a synergistic anti-tumor effect in the murine tumor model with complete inhibition of tumor growth and protected against mouse death ( 138 ).…”

Section: Salmonella Bacteria In Combination Therapiesmentioning

confidence: 99%

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

et al. 2021

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Over the years, conventional cancer treatments, such as chemotherapy with only a limited specificity for tumors, have undergone significant improvement. Moreover, newer therapies such as immunotherapy have undergone a revolution to stimulate the innate as well as adaptive immune responses against the tumor. However, it has been found that tumors can be selectively colonized by certain bacteria, where they can proliferate, and exert direct oncolytic effects as well as stimulating the immune system. Bacterial-mediated cancer therapy (BMCT) is now one example of a hot topic in the antitumor field. Salmonella typhimurium is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. This species has been designed and engineered in order to be used in cancer-targeted therapeutics. S. typhimurium can be used in combination with other treatments such as chemotherapy or radiotherapy for synergistic modification of the tumor microenvironment. Considerable benefits have been shown by using engineered attenuated strains for the diagnosis and treatment of tumors. Some of these treatment approaches have received FDA approval for early-phase clinical trials. This review summarizes the use of Salmonella bacteria for cancer therapy, which could pave the way towards routine clinical application. The benefits of this therapy include an automatic self-targeting ability, and the possibility of genetic manipulation to produce newly engineered attenuated strains. Nevertheless, Salmonella-mediated anticancer therapy has not yet been clinically established, and requires more research before its use in cancer treatment.

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Development of Oxytolerant Salmonella typhimurium Using Radiation Mutation Technology (RMT) for Cancer Therapy

Cited by 19 publications

References 56 publications

The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development

The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development

Bacterial-Based Cancer Therapy (BBCT): Recent Advances, Current Challenges, and Future Prospects for Cancer Immunotherapy

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

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