Medical Applications

Heller, Richard; Teissié, Justin; Rols, Marie-Pierre; Gehl, Julie; Serša, Gregor; Mir, Lluis M.; Neal, Robert E.; Bhonsle, Suyashree; Davalos, Rafael V.; Beebe, Stephen J.; Hargrave, Barbara Y.; Nuccitelli, Richard; Jiang, Chunqi; Čemažar, Maja; Tamzali, Y.; Tozon, Nataša

doi:10.1007/978-4-431-56095-1_5

Cited by 2 publications

(1 citation statement)

References 448 publications

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“…Electroporation technology is a well-established tool for gene electrotransfer including gene therapy by accurate plasmid delivery, drug delivery, and electrochemotherapy. As an FDA-approved clinical method, electroporation has delivered promising outcomes in cancer treatment, tumor ablation and DNA vaccination ( Wong and Neumann, 1982 ; Chang, 1989 ; Mir et al, 1998 ; Neumann et al, 1999 ; Heller et al, 2017 ; Zhang et al, 2017 ; Aycock and Davalos, 2019 ). µsPEF exposure treats cancer by initiating cell death cascades, including apoptosis induction as result of electropermeabilization of biomembranes to small ions.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity

Safaei

Thompson

2022

Front. Bioeng. Biotechnol.

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Electroporation-based technologies using microsecond pulsed electric field (µsPEF) exposures are established as laboratory and clinical tools that permeabilize cell membranes. We demonstrate a µsPEF bioeffect on nucleocytoplasmic import and export of enzymes that regulate genetic expression, histone deacetylases (HDAC) -4 and -5. Their μsPEF-induced nucleocytoplasmic transport depends on presence and absence of extracellular calcium ions (Ca2+) for both MCF7 and CHO-K1 cells. Exposure to 1, 10, 30 and 50 consecutive square wave pulses at 1 Hz and of 100 µs duration with 1.45 kV/cm magnitude leads to translocation of endogenous HDAC4 and HDAC5. We posit that by eliciting a rise in intracellular Ca2+ concentration, a signaling pathway involving kinases, such as Ca2+/CaM-dependent protein kinase II (CaMKII), is activated. This cascade causes nuclear export and import of HDAC4 and HDAC5. The potential of µsPEF exposures to control nucleocytoplasmic transport unlocks future opportunities in epigenetic modification.

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Section: Introductionmentioning

confidence: 99%

Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity

Safaei

Thompson

2022

Front. Bioeng. Biotechnol.

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Pre-clinical investigation of the synergy effect of interleukin-12 gene-electro-transfer during partially irreversible electropermeabilization against melanoma

Pasquet

Bellard

Chabot

et al. 2019

j. immunotherapy cancer

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Background Melanoma is a very aggressive skin tumor that can be cured when diagnosed and treated in its early stages. However, at the time of identification, the tumor is frequently in a metastatic stage. Intensive research is currently ongoing to improve the efficacy of the immune system in eliminating cancer cells. One approach is to boost the activation of cytotoxic T cells by IL-12 cytokine that plays a central role in the activation of the immune system. In parallel, physical methods such as electropermeabilization-based treatments are currently under investigation and show promising results. Methods In this study, we set electrical parameters to induce a partial-irreversible electropermeabilization (pIRE) of melanoma to induce a sufficient cell death and potential release of tumor antigens able to activate immune cells. This protocol mimics the situation where irreversible electropermeabilization is not fully completed. Then, a peritumoral plasmid IL-12 electrotransfer was combined with pIRE treatment. Evaluation of the tumor growth and survival was performed in mouse strains having a different immunological background (C57Bl/6 (WT), nude and C57Bl6 (TLR9−/−)). Results pIRE treatment induced apoptotic cell death and a temporary tumor growth delay in all mouse strains. In C57Bl/6 mice, we showed that peritumoral plasmid IL-12 electrotransfer combined with tumor pIRE treatment induced tumor regression correlating with a local secretion of IL-12 and IFN-γ. This combined treatment induced a growth delay of distant tumors and prevented the emergence of a second tumor in 50% of immunocompetent mice. Conclusions The combination of pIL-12 GET and pIRE not only enhanced survival but could bring a curative effect in wild type mice. This two-step treatment, named Immune-Gene Electro-Therapy (IGET), led to a systemic activation of the adaptive immune system and the development of an anti-tumor immune memory. Electronic supplementary material The online version of this article (10.1186/s40425-019-0638-5) contains supplementary material, which is available to authorized users.

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Medical Applications

Cited by 2 publications

References 448 publications

Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity

Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity

Pre-clinical investigation of the synergy effect of interleukin-12 gene-electro-transfer during partially irreversible electropermeabilization against melanoma

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