Salmonella-Mediated Cancer Therapy: Roles and Potential

Nguyen, Vu H.; Min, Jung‐Joon

doi:10.1007/s13139-016-0415-z

Cited by 46 publications

(39 citation statements)

References 75 publications

(91 reference statements)

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“…The use of bacteria for the development of immunotherapies for cancer has great potential ( 5 – 7 ). Particularly, Salmonella is a facultative anaerobe bacteria that can replicate and accumulate in the tumor microenvironment, which offers the potential to amplify the therapeutic effect at the tumor site, avoiding toxicity in surrounding tissues ( 8 – 10 ). High amount of bacteria are found in necrotic and ischemic regions, which represents an advantage for targeted immunotherapy as these areas are more resistant to radiation and chemotherapy ( 6 , 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, Salmonella is a facultative anaerobe bacteria that can replicate and accumulate in the tumor microenvironment, which offers the potential to amplify the therapeutic effect at the tumor site, avoiding toxicity in surrounding tissues ( 8 – 10 ). High amount of bacteria are found in necrotic and ischemic regions, which represents an advantage for targeted immunotherapy as these areas are more resistant to radiation and chemotherapy ( 6 , 10 – 12 ). Salmonella efficiency can be seen as the result of a dual effect, a direct tumoricidal activity ( 13 , 14 ) and the result of a strong pro-inflammatory response elicited by the bacteria at the tumor site.…”

Section: Introductionmentioning

confidence: 99%

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Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

et al. 2018

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We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients’ conditions. In this work, we assessed the efficacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP–Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immunotherapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

et al. 2018

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“…However, all mice infected with KST0650 or KST0651 exhibited 100% survival for more than 9 days. The LD 50 value (LD 50 = 2 × 10 7 cfu) of KST0650 was similar to that of the well-characterized cancer-targeting Salmonella strain KST0651 (LD 50 = 0.4-2 × 10 7 cfu), which suggested that KST0650 had similar or slightly lower virulence than KST0651 (Table S1) [20][21][22]31 . Based on this result, 1 × 10 6 cfu i.p.…”

Section: Resultsmentioning

confidence: 53%

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

Gao

Jung

Lin

et al. 2020

Sci Rep

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A critical limitation of Salmonella typhimurium (S. typhimurium) as an anti-cancer agent is the loss of their invasive or replicative activities, which results in no or less delivery of anti-cancer agents inside cancer cells in cancer therapy. Here we developed an oxytolerant attenuated Salmonella strain (KST0650) from the parental KST0649 (ΔptsIΔcrr) strain using radiation mutation technology (RMT). The oxytolerant KST0650 strain possessed 20-times higher replication activity in CT26 cancer cells and was less virulent than KST0649. Furthermore, KST0650 migrated effectively into tumor tissues in mice. KST0650 was further equipped with a plasmid harboring a spliced form of the intracellular proapoptotic protein sATF6, and the expression of sATF6 was controlled by the radiation-inducible recN promoter. The new strain was named as KST0652, in which sATF6 protein expression was induced in response to radiation in a dose-dependent manner. This strain was effectively delivered inside cancer cells and tumor tissues via the Salmonella type III secretion system (T3SS). In addition, combination treatment with KST0652 and radiation showed a synergistic anti-tumor effect in murine tumor model with complete inhibition of tumor growth and protection against death. In conclusion, we showed that RMT can be used to effectively develop an anti-tumor Salmonella strain for delivering anti-cancer agents inside tumors.Spontaneous mutations have been extensively used as sources of novel genetic diversity for selecting new improved organisms 1,2 . After the discovery of X-rays and γ-rays, ionizing radiation (IR)-induced mutation breeding is being widely used to generate genetic variability in various organisms 3,4 . After penetrating inside tissues, γ-rays directly disrupt DNA via deposition of energy, or indirectly via ionization, which generates free radicals from radiolysis of water 5-7 . Even though chemical mutagens and ultraviolet irradiation has been widely used for producing bacterial mutants, deletions and insertions are limitedly introduced in the genome. However, the effects of IR cause various types of random DNA mutations including deletions, insertions, and point mutations during DNA repair. The Food and Agriculture Organization of the United Nations (FAO) and the International Atomic Energy Agency (IAEA) Joint Mutant Varieties Database indicated that over 87% of 3,200 mutant variants in 214 plant species, which were developed using RMT, have been released worldwide 8,9 . However, the use of this technique in bacteria is limited, especially for bacteria that are used for medical applications.Salmonella as a potential anti-cancer tool is valuable for treating cancer because of its selective colonizing and proliferative abilities in nonhypoxic and hypoxic regions 10-12 . However, the high virulence of Salmonella limits its application in cancer therapy. Hence, methods of developing attenuated Salmonella strains without

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“…The most common bacteria used in this field are the genera Salmonella , Clostridium , Bifidobacterium , Lactobacillus , Escherichia , Pseudomonas , Caulobacter , Listeria , Proteus, and Streptococcus . The use of three species of bacteria, Clostridia , Bifidobacteria , and Salmonellae as vectors for delivering or expressing tumor suppressor genes, anti‐angiogenic genes, suicide genes, or tumor‐associated antigens has been tested in animal models bearing various tumors . Some clinical trials have already been conducted displaying partial responses, and thus further investigation should be performed in humans .…”

Section: Bacteria In Cancer Therapymentioning

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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Salmonella-Mediated Cancer Therapy: Roles and Potential

Cited by 46 publications

References 75 publications

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

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

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

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