siRNA targeting PD-L1 delivered with attenuated Salmonella enhanced the anti-tumor effect of lenvatinib on mice bearing Hepatocellular carcinoma

Chen, Pengfei; Li, Yingjing; Wei, Pengkun; Liang, Lirui; Li, Baozhu; Cao, Yuhao; Han, Xinwei; Wang, Yanling; Duan, Xin; Jia, Hui‐Zhen; Zhao, Tieuso; Ren, Jianzhuang

doi:10.1016/j.intimp.2022.109127

Cited by 11 publications

(7 citation statements)

References 37 publications

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“…The cell lines were tested for mycoplasma contamination by PCR-based method and confirmed negative for mycoplasma. The attenuated Salmonella typhimurium and strains carrying Scramble and siRNA-PD-L1 plasmids were previously constructed and are also stored in the same laboratory [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement

Jia,

Wei,

Zhou

et al. 2023

Cell Death Discov.

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Hepatocellular carcinoma (HCC), the most prevalent type of aggressive liver cancer, accounts for the majority of liver cancer diagnoses and fatalities. Despite recent advancements in HCC treatment, it remains one of the deadliest cancers. Radiation therapy (RT) is among the locoregional therapy modalities employed to treat unresectable or medically inoperable HCC. However, radioresistance poses a significant challenge. It has been demonstrated that RT induced the upregulation of programmed death ligand 1 (PD-L1) on tumor cells, which may affect response to PD-1-based immunotherapy, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. Here, we utilized attenuated Salmonella as a carrier to explore whether attenuated Salmonella carrying siRNA-PD-L1 could effectively enhance the antitumor effect of radiotherapy on HCC-bearing mice. Our results showed that a combination of siRNA-PD-L1 and radiotherapy had a synergistic antitumor effect by inhibiting the expression of PD-L1 induced by radiation therapy. Mechanistic insights indicated that the combination treatment significantly suppressed tumor cell proliferation, promoted cell apoptosis, and stimulated immune cell infiltration and activation in tumor tissues. Additionally, the combination treatment increased the ratios of CD4+ T, CD8+ T, and NK cells from the spleen in tumor-bearing mice. This study presents a novel therapeutic strategy for HCC treatment, especially for patients with RT resistance.

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Section: Methodsmentioning

confidence: 99%

Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement

Jia,

Wei,

Zhou

et al. 2023

Cell Death Discov.

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“… 128 For RNA-related bacterial therapy, a study demonstrated the successful delivery of siRNA-PD-L1 using attenuated Salmonella , and the combination of lenvatinib effectively inhibited tumor growth and induced increased apoptosis in tumor cells. 129 Furthermore, it was discovered that attenuated S. Typhimurium could effectively deliver shRNA-expressing vectors targeting STAT3 to hepatocellular carcinoma (HCC) cells and trigger RNA interference in vivo, leading to a substantial delay and reduction in HCC. 130 Additional studies also shown the efficacy of using Salmonella as a drug delivery vehicle for administering proteins.…”

Section: Application Of Engineered Bacteria In Tumor Therapymentioning

confidence: 99%

Promising dawn in tumor microenvironment therapy: engineering oral bacteria

Wang,

Sun,

Hua

et al. 2024

Int J Oral Sci

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Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

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“…For example, Chen and co-workers used siRNA to silence PD-L1 genes and reported a subsequent inhibition of the tumor growth of an H22 HCC model in mice, which was mediated by an increase in the infiltration of T cells, an increase in the ratio of T cells in the spleen, an increase in the number of granzyme B + T cells, as well as a synergistic interaction that potentiated the effects of the multiple kinase inhibitor, Lenvatinib. 128…”

Section: Dovepressmentioning

confidence: 99%

Understanding Gene Involvement in Hepatocellular Carcinoma: Implications for Gene Therapy and Personalized Medicine

Younis,

Harashima

2024

PGPM

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Hepatocellular carcinoma (HCC) is the dominant type of liver cancers and is one of the deadliest health threats globally. The conventional therapeutic options for HCC are hampered by low efficiency and intolerable side effects. Gene therapy, however, now offers hope for the treatment of many disorders previously considered incurable, and gene therapy is beginning to address many of the shortcomings of conventional therapies. Herein, we summarize the involvement of genes in the pathogenesis and prognosis of HCC, with a special focus on dysregulated signaling pathways, genes involved in immune evasion, and non-coding RNAs as novel two-edged players, which collectively offer potential targets for the gene therapy of HCC. Herein, the opportunities and challenges of HCC gene therapy are discussed. These include innovative therapies such as genome editing and cell therapies. Moreover, advanced gene delivery technologies that recruit nanomedicines for use in gene therapy for HCC are highlighted. Finally, suggestions are offered for improved clinical translation and future directions in this area of endeavor.

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siRNA targeting PD-L1 delivered with attenuated Salmonella enhanced the anti-tumor effect of lenvatinib on mice bearing Hepatocellular carcinoma

Cited by 11 publications

References 37 publications

Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement

Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement

Promising dawn in tumor microenvironment therapy: engineering oral bacteria

Understanding Gene Involvement in Hepatocellular Carcinoma: Implications for Gene Therapy and Personalized Medicine

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