Intratumoral STING Agonist Injection Combined with Irreversible Electroporation Delays Tumor Growth in a Model of Hepatocarcinoma

Lasarte-Cía, Aritz; Lozano, Teresa; Cano, David; Martín-Otal, Celia; Navarro, Flor; Gorraiz, Marta; Casares, Noëlia; Vivas, Isabel; Lasarte, Juan José

doi:10.1155/2021/8852233

Cited by 11 publications

(14 citation statements)

References 44 publications

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“…Go et al [ 36 ] used a murine lung cancer model to demonstrate that combination STING/IRE resulted in an increase in activated DCs, CD4+ and CD8+ T cells, and M1 macrophages in the TME, and a decrease in M2 immunosuppressive macrophages. Data from Lasarte-Cia et al [ 37 ] showed similar results in melanoma and HCC models. Both studies reported substantial tumor regression in the combination group.…”

Section: Therapeutic Strategies For Combination Hit-it and Tumor Abla...mentioning

confidence: 65%

Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Senders

Martin

2022

Cancers

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Several intratumoral immunotherapeutic agents have shown efficacy in controlling local disease; however, their ability to induce a durable systemic immune response is limited. Likewise, tumor ablation is well-established due to its role in local disease control but generally produces only a modest immunogenic effect. It has recently been recognized, however, that there is potential synergy between these two modalities and their distinct mechanisms of immune modulation. The aim of this review is to evaluate the existing data regarding multimodality therapy with intratumoral immunotherapy and tumor ablation. We discuss the rationale for this therapeutic approach, highlight novel combinations, and address the challenges to their clinical utility. There is substantial evidence that combination therapy with intratumoral immunotherapy and tumor ablation can potentiate durable systemic immune responses and should be further evaluated in the clinical setting.

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Section: Therapeutic Strategies For Combination Hit-it and Tumor Abla...mentioning

confidence: 65%

Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Senders

Martin

2022

Cancers

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“…In addition, some animal studies have shown that IRE combined with immune checkpoint inhibitors (ICIs) and immunostimulants can augment immune status and inhibit the growth of tumors transplanted in the liver (120,121), skin (121), and prostate (21), yielding extended survival benefits. Two clinical studies found that the IRE and allogenic natural killer cell immunotherapy combination is a promising strategy to enhance antitumor efficacy in advanced hepatocellular carcinoma patients (122,123). These encouraging results will prompt the development of a combination therapeutic strategy for the treatment of cancer patients refractory to other therapies.…”

Section: Therapeutic Effects Of Ire Combined With Immunotherapy On Solid Tumorsmentioning

confidence: 99%

Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors

Zhang

Han

et al. 2022

Front. Immunol.

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Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an “in-situ tumor vaccine,” inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.

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“…Preclinical studies have investigated a wide range of immunotherapies administered in various combinations with IRE, including anti-CTLA-4 [ 149 ], anti-PD-1 [ 87 , 150 ], TLR agonists [ 96 , 151 ], M1 oncolytic virus [ 90 ], and STING agonist [ 152 , 153 ]. Studies have been focused mainly on pancreatic cancer and to a lesser extent hepatocellular carcinoma, melanoma, prostate cancer, and breast cancer.…”

Section: The Synergy Of Electroporation and Immunotherapymentioning

confidence: 99%

“…Moreover, this combination regimen induced tumor infiltration of CD8 + and CD4 + T cells and increased the ratio of the anti-tumor M1 macrophages, while reducing both the number of Tregs cells and MDSCs [ 96 ]. IRE + STING agonist showed limited efficacy in melanoma [ 152 ] and great efficacy in hepatocellular carcinoma [ 152 ]. Further, in a Lewis lung carcinoma model, IRE + STING increased the tumor infiltration of CD8 + and CD4 + T cells and induced a shift in the M1/M2 macrophage ratio towards the anti-tumor M1 phenotype [ 153 ].…”

Section: The Synergy Of Electroporation and Immunotherapymentioning

confidence: 99%

Electroporation and Immunotherapy—Unleashing the Abscopal Effect

Justesen

Orhan

Raskov

et al. 2022

Cancers

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The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells. With the dawn of the immunotherapy era, the potential of combining ECT and IRE with immunotherapy has led to the launch of numerous studies. Data from the first clinical trials are promising, and new combination regimes might change the way we treat tumors characterized by low immunogenicity and high levels of immunosuppression, such as melanoma and pancreatic cancer. In this review we will give an introduction to ECT and IRE and discuss the impact on the immune system. Additionally, we will present the results of clinical and preclinical trials, investigating the combination of electroporation modalities and immunotherapy.

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Intratumoral STING Agonist Injection Combined with Irreversible Electroporation Delays Tumor Growth in a Model of Hepatocarcinoma

Cited by 11 publications

References 44 publications

Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors

Electroporation and Immunotherapy—Unleashing the Abscopal Effect

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