<i>Salmonella</i>-Mediated Cancer Therapy: An Innovative Therapeutic Strategy

Mi, Ze; Feng, Zhichao; Li, Cheng; Xiao, Yang; Ma, Mengtian; Rong, Pengfei

doi:10.7150/jca.32650

Cited by 54 publications

(64 citation statements)

References 98 publications

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“…Additionally, Salmonella is well-known to preferentially accumulate within tumors, especially in the nonhypoxic and hypoxic regions. Even some Salmonella strains is being evaluated in a phase I clinical trial in humans ( Mi et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Salmonella-innovative targeting carrier: Loading with doxorubicin for cancer treatment

Rabea

Alanazi

Ashour

et al. 2020

Saudi Pharmaceutical Journal

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Cell- based targeted delivery is recently gain attention as a promising platform for delivery of anticancer drug in selective and efficient manner. As a new biotechnology platform, bacterial ghosts (BGs) have novel biomedical application as targeted drug delivery system (TDDS). In the current work, Salmonellas’ BGs was utilized for the first time as hepatocellular cancer (HCC) in-vitro targeted delivery system. Successful BGs loading and accurate analysis of doxorubicin (DOX) were necessary steps for testing the applicability of DOX loaded BGs in targeting the liver cancer cells. Loading capacity was maximized to reach 27.5 µg/mg (27.5% encapsulation efficiency), by incubation of 10 mg BGs with 1 mg DOX at pH 9 in constant temperature (25 °C) for 10 min. In-vitro release study of DOX loaded BGs showed a sustained release (182 h) obeying Higuchi sustained kinetic release model. The death rate (tested by MTT assay) of HepG2 reached to 64.5% by using of 4 μg/ml, while it was about 51% using the same concentration of the free DOX ( P value < 0.0001 One-way ANOVA analysis). The proliferative inhibitory concentration (IC50) of the DOX combined formula was 1.328 µg/ml that was about one third of the IC50 of the free DOX (3.374 μg/ml). Apoptosis analysis (tested by flow-cytometry) showed more accumulation in early apoptosis (8.3%) and late apoptosis/necrosis (91%) by applying 1 μg/ml BGs combined DOX, while 1 μg/ml free DOX showed 33.4% of cells in early apoptosis and 39.3% in late apoptosis/necrosis, ( P value ˃ 0.05: one-way ANOVA). In conclusion, DOX loaded Salmonellas’ BGs are successfully prepared and tested in vivo with promising potential as hepatocellular cancer (HCC) targeted delivery system.

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Section: Resultsmentioning

confidence: 99%

Salmonella-innovative targeting carrier: Loading with doxorubicin for cancer treatment

Rabea

Alanazi

Ashour

et al. 2020

Saudi Pharmaceutical Journal

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“…Indeed, the use of PDOX models has been documented in human melanoma, pancreatic cancer, osteosarcoma, and gastrointestinal stromal tumor [38]. However, the problems in Salmonella need to be further confirmed for clinical feasibility, dose-limiting toxicity, tumor localization, inflammatory reaction, and host immunity [39,40].…”

Section: Discussionmentioning

confidence: 99%

Salmonella Breaks Tumor Immune Tolerance by Downregulating Tumor Programmed Death-Ligand 1 Expression

Chen

Pangilinan

Lee

2019

Cancers

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Immunotherapy is becoming a popular treatment modality in combat against cancer, one of the world’s leading health problems. While tumor cells influence host immunity via expressing immune inhibitory signaling proteins, some bacteria possess immunomodulatory activities that counter the symptoms of tumors. The accumulation of Salmonella in tumor sites influences tumor protein expression, resulting in T cell infiltration. However, the molecular mechanism by which Salmonella activates T cells remains elusive. Many tumors have been reported to have high expressions of programmed death-ligand 1 (PD-L1), which is an important immune checkpoint molecule involved in tumor immune escape. In this study, Salmonella reduced the expression of PD-L1 in tumor cells. The expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and the phospho-p70 ribosomal s6 kinase (P-p70s6K) pathway were revealed to be involved in the Salmonella-mediated downregulation of PD-L1. In a tumor-T cell coculture system, Salmonella increased T cell number and reduced T cell apoptosis. Systemic administration of Salmonella reduced the expressions of PD-L-1 in tumor-bearing mice. In addition, tumor growth was significantly inhibited along with an enhanced T cell infiltration following Salmonella treatment. These findings suggest that Salmonella acts upon the immune checkpoint, primarily PD-L1, to incapacitate protumor effects and thereby inhibit tumor growth.

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“…Active division of tumor cells and the necrosis inside tumors provide a conducive environment for Salmonellae ( 25 ). Salmonella accumulating in tumors deprive extracellular nutrients from tumor cells ( 38 ), which promotes apoptosis in tumor cells ( 39 ). Salmonella influxes into solid tumors up-regulates the production and release of TNF-α, which leads to tumor hemorrhage and Salmonella invasion, and eventually inhibits tumor angiogenesis ( 34 ).…”

Section: Salmonella In Cancer Therapymentioning

confidence: 99%

Perspectives on Oncolytic Salmonella in Cancer Immunotherapy—A Promising Strategy

et al. 2021

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Since the first reported spontaneous regression of tumors in patients with streptococcus infection, cancer biological therapy was born and it evolved into today’s immunotherapy over the last century. Although the original strategy was unable to impart maximal therapeutic benefit at the beginning, it laid the foundations for the development of immune checkpoint blockade and CAR-T which are currently used for cancer treatment in the clinics. However, clinical applications have shown that current cancer immunotherapy can cause a series of adverse reactions and are captious for patients with preexisting autoimmune disorders. Salmonellae was first reported to exert antitumor effect in 1935. Until now, numerous studies have proved its potency as an antitumor agent in the near future. In this review, we summarize the currently available data on the antitumor effects of Salmonella, and discussed a possibility of integrating Salmonella into cancer immunotherapy to overcome current obstacles.

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Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy

Cited by 54 publications

References 98 publications

Salmonella-innovative targeting carrier: Loading with doxorubicin for cancer treatment

Salmonella-innovative targeting carrier: Loading with doxorubicin for cancer treatment

Salmonella Breaks Tumor Immune Tolerance by Downregulating Tumor Programmed Death-Ligand 1 Expression

Perspectives on Oncolytic Salmonella in Cancer Immunotherapy—A Promising Strategy

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