Attenuated<i>Salmonella VNP20009 mutant</i>(<i>ΔhtrA</i>) is a promising candidate for bacteria-mediated tumour therapy in hosts with TNFR1 deficiency

Xu, Wenxi; Zhou, Tian; Zhou, Jihong; Qiang, Zexuan; Zhang, J.; Hua, Zichun

doi:10.1111/lam.12999

Cited by 16 publications

(15 citation statements)

References 21 publications

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“…Although viruses have been utilized for genetic therapeutics to permanently overexpress protein drugs or interfering RNAs in target cells 5,6 , the utility of viruses is largely limited by their rapid spread, difficulty to eliminate and potential to cause serious infections. Bacteria, another group of broadly used microorganisms, are relatively manipulable and safe, because they are easy to be modified genetically and can be controlled by antibiotics 7–9 . More importantly, various bacterial species are able to colonize specific body sites of mammalian hosts, for example the gut or the skin, as well as disease sites including abscesses and tumor tissues 8,10–14 .…”

Section: Introductionmentioning

confidence: 99%

Camouflaging bacteria by wrapping with cell membranes

et al. 2019

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Bacteria have been extensively utilized for bioimaging, diagnosis and therapy given their unique characteristics including genetic manipulation, rapid proliferation and disease site targeting specificity. However, clinical translation of bacteria for these applications has been largely restricted by their unavoidable side effects and low treatment efficacies. Engineered bacteria for biomedical applications ideally need to generate only a low inflammatory response, show slow elimination by macrophages, low accumulation in normal organs, and almost unchanged inherent bioactivities. Here we describe a set of stealth bacteria, cell membrane coated bacteria (CMCB), meeting these requirement. Our findings are supported by evaluation in multiple mice models and ultimately demonstrate the potential of CMCB to serve as efficient tumor imaging agents. Stealth bacteria wrapped up with cell membranes have the potential for a myriad of bacterial-mediated biomedical applications.

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Section: Introductionmentioning

confidence: 99%

Camouflaging bacteria by wrapping with cell membranes

et al. 2019

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“…In previous studies, many organisms have shown prominent anti-tumor effects in various cancer models. These include Listeria monocytogenes, Salmonella typhimurium and many other programmable bacteria [19][20][21][22][23][24][25], the oncolytic virus Talimogene laherparepvec [26], cowpea mosaic virus [27][28][29][30], yellow fever vaccine 17D [31] and the artificial attenuated parasite Toxoplasma gondii [32][33][34][35][36][37], all of which have been reported to be able to inhibit the growth or metastasis of tumors as well as improve prognosis. Genetic manipulation enables the generation of avirulent or attenuated microorganisms that can induce powerful immune responses, making them effective immune-stimulating anti-tumor agents.…”

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confidence: 99%

A uracil auxotroph Toxoplasma gondii exerting immunomodulation to inhibit breast cancer growth and metastasis

Yao

Jiang

et al. 2021

Parasites Vectors

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Background Breast cancer is the most common cause of cancer-related death among women, and prognosis is especially poor for patients with triple-negative breast cancer (TNBC); therefore, there is an urgent need for new effective therapies. Recent studies have demonstrated that the uracil auxotroph Toxoplasma gondii vaccine displays anti-tumor effects. Here, we examined the immunotherapy effects of an attenuated uracil auxotroph strain of T. gondii against 4T1 murine breast cancer. Methods We constructed a uracil auxotroph T. gondii RH strain via orotidine 5′-monophosphate decarboxylase gene deletion (RH-Δompdc) with CRISPR/Cas9 technology. The strain’s virulence in the T. gondii-infected mice was determined in vitro and in vivo by parasite replication assay, plaque assay, parasite burden detection in mice peritoneal fluids and survival analysis. The immunomodulation ability of the strain was evaluated by cytokine detection. Its anti-tumor effect was evaluated after its in situ inoculation into 4T1 tumors in a mouse model; the tumor volume was measured, and the 4T1 lung metastasis was detected by hematoxylin and eosin and Ki67 antibody staining, and the cytokine levels were measured by an enzyme-linked immunosorbent assay. Results The RH-Δompdc strain proliferated normally when supplemented with uracil, but it was unable to propagate without the addition of uracil and in vivo, which suggested that it was avirulent to the hosts. This mutant showed vaccine characteristics that could induce intense immune responses both in vitro and in vivo by significantly boosting the expression of inflammatory cytokines. Inoculation of RH-Δompdc in situ into the 4T1 tumor inhibited tumor growth, reduced lung metastasis, promoted the survival of the tumor-bearing mice and increased the secretion of Th1 cytokines, including interleukin-12 (IL-12) and interferon-γ (INF-δ), in both the serum and tumor microenvironment (TME). Conclusion Inoculation of the uracil auxotroph RH-Δompdc directly into the 4T1 tumor stimulated anti-infection and anti-tumor immunity in mice, and resulted in inhibition of tumor growth and metastasis, promotion of the survival of the tumor-bearing mice and increased secretion of IL-12 and IFN-γ in both the serum and TME. Our findings suggest that the immunomodulation caused by RH-Δompdc could be a potential anti-tumor strategy. Graphical abstract

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“…Recently, VNP20009 has been sequenced for other genes to improve tumor targeting. Aside from the known purI and msbB gene deletions, other mutations have also been found, including a 108-kb Suwwan deletion, 50 nonsynonymous SNPs, a purM deletion and a derivative ∆htrA 29, 30. More research is needed to prove their effectiveness and stability.…”

Section: S Typhimurium Laboratory Strains For Cancer Therapymentioning

confidence: 99%

Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy

Feng

et al. 2019

J. Cancer

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Bacterial-mediated cancer therapy (BMCT) has become a hot topic in the area of antitumor treatment. Salmonella has been recommended to specifically colonize and proliferate inside tumors and even inhibit tumor growth. Salmonella typhimurium (S. typhimurium) is one of the most promising mediators, which can be easily manipulated. S. typhimurium has been engineered and designed as cancer-targeting therapeutics, and can be improved by combining with other therapeutic methods, e.g. chemotherapy and radiotherapy, which regulate the tumor microenvironment synergistically. In view of all these strengths, the engineered attenuated strains have significant advantages for tumor diagnosis and treatment. This treatment has also been approved by the FDA for clinical trial. In this review, we summarized the recent progress and research in the field of Salmonella-mediated cancer therapy.

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AttenuatedSalmonella VNP20009 mutant(ΔhtrA) is a promising candidate for bacteria-mediated tumour therapy in hosts with TNFR1 deficiency

Cited by 16 publications

References 21 publications

Camouflaging bacteria by wrapping with cell membranes

Camouflaging bacteria by wrapping with cell membranes

A uracil auxotroph Toxoplasma gondii exerting immunomodulation to inhibit breast cancer growth and metastasis

Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy

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