Safety and Short-Term Efficacy of Irreversible Electroporation and Allogenic Natural Killer Cell Immunotherapy Combination in the Treatment of Patients with Unresectable Primary Liver Cancer

Yang, Yumei; Qin, Zilin; Du, Duanming; Wu, Yue; Qiu, Shaofu; Mu, Feng; Xu, Kengcheng; Chen, Jibing

doi:10.1007/s00270-018-2069-y

Cited by 36 publications

(33 citation statements)

References 36 publications

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“…130 This initial study, along with a similar investigation for patients with unresectable liver cancer, indicates that IRE could play a ''priming'' role by preparing the tumor microenvironment for effective exploitation by immunotherapy. 137 Further clinical examination has shown that immune modulation occurs quickly after IRE and that attenuation of the highly immunosuppressive environment, as seen by a reduction in regulatory T cells, can be achieved for at least 2 weeks. 138,139 These results are supported by the finding that IRE and anti-PD1 immunotherapy work synergistically to improve survival in a murine model of pancreatic cancer.…”

Section: Immune Modulation and Synergy With Immunotherapymentioning

confidence: 99%

Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology

2019

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Irreversible electroporation (IRE) has established a clinical niche as an alternative to thermal ablation for the eradication of unresectable tumors, particularly those near critical vascular structures. IRE has been used in over 50 independent clinical trials and has shown clinical success when used as a standalone treatment and as a single component within combinatorial treatment paradigms. Recently, many studies evaluating IRE in larger patient cohorts and alongside other novel therapies have been reported. Here, we present the basic principles of reversible electroporation and IRE followed by a review of preclinical and clinical data with a focus on tumors in three organ systems in which IRE has shown great promise: the prostate, pancreas, and liver. Finally, we discuss alternative and future developments, which will likely further advance the use of IRE in the clinic.

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Section: Immune Modulation and Synergy With Immunotherapymentioning

confidence: 99%

Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology

2019

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“…In this study including 40 patients, increased OS was observed in the combination therapy group compared with irreversible electroporation monotherapy group (10.1 vs. 8.9 months, p = 0.0078) [86]. In 2019, a similar study conducted in 40 unresectable primary liver cancer patients reported that patients who received combination therapy exhibited superior median PFS and OS compared to those who received irreversible electroporation monotherapy (PFS 15.1 vs. 10.6 months, p < 0.05; OS 17.9 vs. 23.2 months, p < 0.05) [87]. In this study, the allogeneic NK cells were donated by KIR-HLA mismatching relatives and expanded using the in vitro preparation kit (HANK Bioengineering Co., Ltd, Shenzhen, China) [87].…”

Section: Current Nk Cell Therapy In Solid Tumorsmentioning

confidence: 99%

Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

Lee

Kwack

et al. 2019

Cancers

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In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic NK cell therapy, the mismatch between the killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) can be harnessed to increase the antitumor activity. However, the allogeneic NK cells cause more adverse events and can be rejected by the host immune system after repeated injections. In this regard, the autologous NK cell therapy is safer. This article reviews the published results of clinical trials and discusses strategies to enhance the efficacy of the NK cell therapy. The difference in immunophenotype of the ex vivo expanded NK cells resulted from different culture methods may affect the final efficacy. Furthermore, currently available standard anticancer therapy, molecularly targeted agents, and checkpoint inhibitors may directly or indirectly enhance the efficacy of NK cell therapy. A recent study discovered that NK cell specific genetic defects are closely associated with the tumor immune microenvironment that determines clinical outcomes. This finding warrants future investigations to find the implication of NK cell specific genetic defects in cancer development and treatment, and NK cell deficiency syndrome should be revisited to enhance our understanding. Overall, it is clear that NK cell therapy is safe and promises a new paradigm for the treatment of solid tumors.

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“… 41 Some studies even suggest that immunogenic effect of IRE is more pronounced than in other ablation therapies like radiofrequency ablation 31 and cryoablation. 32 Evidence suggests that administration of immune-stimulating molecules can even enhance the local effectiveness of ECT 35 and IRE 29 , 42 , 43 , 44 allowing simultaneous treatment of distant tumors.…”

Section: Introductionmentioning

confidence: 99%

Analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro

Polajžer

Jarm

Miklavčič

2020

Radiology and Oncology

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BackgroundTumor cells can die via immunogenic cell death pathway, in which damage-associated molecular pattern molecules (DAMPs) are released from the cells. These molecules activate cells involved in the immune response. Both innate and adaptive immune response can be activated, causing a destruction of the remaining infected cells. Activation of immune response is also an important component of tumor treatment with electrochemotherapy (ECT) and irreversible electroporation (IRE). We thus explored, if and when specific DAMPs are released as a consequence of electroporation in vitro.Materials and methodsIn this in vitro study, 100 μs long electric pulses were applied to a suspension of Chinese hamster ovary cells. The release of DAMPs – specifically: adenosine triphosphate (ATP), calreticulin, nucleic acids and uric acid was investigated at different time points after exposing the cells to electric pulses of different amplitudes. The release of DAMPs was statistically correlated with cell permeabilization and cell survival, e.g. reversible and irreversible electroporation.ResultsIn general, the release of DAMPs increases with increasing pulse amplitude. Concentration of DAMPs depend on the time interval between exposure of the cells to pulses and the analysis. Concentrations of most DAMPs correlate strongly with cell death. However, we detected no uric acid in the investigated samples.ConclusionsRelease of DAMPs can serve as a marker for prediction of cell death. Since the stability of certain DAMPs is time dependent, this should be considered when designing protocols for detecting DAMPs after electric pulse treatment.

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Safety and Short-Term Efficacy of Irreversible Electroporation and Allogenic Natural Killer Cell Immunotherapy Combination in the Treatment of Patients with Unresectable Primary Liver Cancer

Abstract: Our data suggest a novel, promising combination therapy using IRE and allogenic NK cell immunotherapy. Larger clinical trials are required to confirm these conclusions.

Cited by 36 publications

References 36 publications

Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology

Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology

Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

Analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro

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