Radiotherapy combined with an engineered &lt;i&gt;Salmonella typhimurium&lt;/i&gt; inhibits tumor growth in a mouse model of colon cancer

Liu, Xiande; Jiang, Sanyuan; Li, Piao; Yuan, Feng

doi:10.1538/expanim.16-0033

Cited by 53 publications

(37 citation statements)

References 15 publications

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“…Because multiple bacteria strains expressing different therapeutics will compete for resources within a tumor, reducing the effective dosage of each therapeutic, the BSCC system can assess how combination therapy will perform when increasing the number of bacterial therapies. In addition, the broad applicability of the spheroid model can be employed to assess combinations of bacterial therapy with chemotherapy (42) and radiotherapy (43) to improve on existing treatments. The BSCC system is precisely suited to quantitatively explore large libraries and combinatorial strategies in a high-throughput fashion.…”

Section: Discussionmentioning

confidence: 99%

Rapid screening of engineered microbial therapies in a 3D multicellular model

Harimoto

Singer

Velazquez

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Synthetic biology is transforming therapeutic paradigms by engineering living cells and microbes to intelligently sense and respond to diseases including inflammation, infections, metabolic disorders, and cancer. However, the ability to rapidly engineer new therapies far outpaces the throughput of animal-based testing regimes, creating a major bottleneck for clinical translation. In vitro approaches to address this challenge have been limited in scalability and broad applicability. Here, we present a bacteria-in-spheroid coculture (BSCC) platform that simultaneously tests host species, therapeutic payloads, and synthetic gene circuits of engineered bacteria within multicellular spheroids over a timescale of weeks. Long-term monitoring of bacterial dynamics and disease progression enables quantitative comparison of critical therapeutic parameters such as efficacy and biocontainment. Specifically, we screen Salmonella typhimurium strains expressing and delivering a library of antitumor therapeutic molecules via several synthetic gene circuits. We identify candidates exhibiting significant tumor reduction and demonstrate high similarity in their efficacies, using a syngeneic mouse model. Last, we show that our platform can be expanded to dynamically profile diverse microbial species including Listeria monocytogenes, Proteus mirabilis, and Escherichia coli in various host cell types. This high-throughput framework may serve to accelerate synthetic biology for clinical applications and for understanding the host–microbe interactions in disease sites.

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Section: Discussionmentioning

confidence: 99%

Rapid screening of engineered microbial therapies in a 3D multicellular model

Harimoto

Singer

Velazquez

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Recently, a number of studies have developed a new approach for cancer therapy using genetically engineered bacteria designed to express reporter genes, cytotoxic protein and/or anticancer agents, and tumor‐specific antigens . It has been found that genetically modified bacteria can have a more significant multiplication in tumors than in normal tissues . The ability of Salmonella typhimurium serovar VNP20009 and Clostridium butyricum M55 to selectively colonize tumors has allowed them to be used as delivery vectors in mouse tumor models, without severe immune responses or toxic side effects.…”

Section: Genetically Modified Bacteria In Cancer Therapymentioning

confidence: 99%

“…A serious drawback of radiotherapy is that it is not clear whether the radiation affects cytotoxin‐expressing Salmonella that has localized in the tumor. Liu et al reported that the combination of radiotherapy and bacterial therapy using engineered S typhimurium ∆ppGpp reduced tumor growth compared with bacterial therapy alone. In addition, the researchers recently showed that the agonist of toll‐like receptor 5 (TLR5), called bacterial flagellin, as well as CBLB502 (its pharmacologically optimized derivative) could protect primates and rodents from gastrointestinal and hematopoietic radiation syndromes induced by total body irradiation .…”

Section: Combination Of Bacteriotherapy With Radiotherapymentioning

confidence: 99%

Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities

et al. 2019

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Successful treatment of cancer remains a challenge, due to the unique pathophysiology of solid tumors, and the predictable emergence of resistance. Traditional methods for cancer therapy including radiotherapy, chemotherapy, and immunotherapy all have their own limitations. A novel approach is bacteriotherapy, either used alone, or in combination with conventional methods, has shown a positive effect on regression of tumors and inhibition of metastasis. Bacteria‐assisted tumor‐targeted therapy used as therapeutic/gene/drug delivery vehicles has great promise in the treatment of tumors. The use of bacteria only, or in combination with conventional methods was found to be effective in some experimental models of cancer (tumor regression and increased survival rate). In this article, we reviewed the major advantages, challenges, and prospective directions for combinations of bacteria with conventional methods for tumor therapy.

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“…Cytolysins are generally derived from Escherichia coli or Staphylococcus aureus [ 4 ]. Studies have demonstrated that mice on treating with S. typhimurium or E. coli strains expressing the ClyA toxin demonstrated tumor growth inhibition [ 11 , 17 ]. Jiang et al engineered cytolysin producing E. coli strain K-12 which in combination with radiotherapy retarded tumor growth in mice with tumors derived from murine CT26 colon cancer and prevented its metastatic spread [ 11 ].…”

Section: Mechanism Of Tumor Suppressionmentioning

confidence: 99%

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

Sawant

Patil

Gupta

et al. 2020

IJMS

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Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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Radiotherapy combined with an engineered <i>Salmonella typhimurium</i> inhibits tumor growth in a mouse model of colon cancer

Cited by 53 publications

References 15 publications

Rapid screening of engineered microbial therapies in a 3D multicellular model

Rapid screening of engineered microbial therapies in a 3D multicellular model

Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

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