Effects of Electrochemotherapy on Immunologically Important Modifications in Tumor Cells

Kesar, Ursa; Markelc, Boštjan; Jesenko, Tanja; Valentinuzzi, Katja Ursic; Čemažar, Maja; Strojan, Primož; Serša, Gregor

doi:10.3390/vaccines11050925

Cited by 6 publications

(5 citation statements)

References 62 publications

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“… 20 , 48 , 80 , 81 Electrochemotherapy can induce immunogenic cell death through the release of damage-associated molecular patterns (DAMP) which serve as a signal to stimulate the immune system. 82 , 83 , 84 Massive liberation of tumor antigens together with DAMPs can activate the antigen-presenting dendritic cells. 85 , 86 Multiple studies in canine 87 , 88 , 89 , in mice 47 and human patients 90 have thus been testing ECT in combination with gene electrotransfer (GET) of plasmid DNA encoding for interleukin-12 (IL-12), which stimulates the immune system.…”

Section: Discussionmentioning

confidence: 99%

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an in vitro study

Scuderi,

Dermol-Cerne,

Scancar

et al. 2024

Radiology and Oncology

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Background Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipolar pulses has been shown to mitigate pain and muscle contractions. Conversely, the use of millisecond pulses is interesting when combining ECT with gene electrotransfer for the uptake of DNA-encoding proteins that stimulate the immune response with the aim of converting ECT from a local to systemic treatment. Therefore, the aim of this study was to investigate how alternative types of pulses affect the efficiency of the ECT. Materials and methods We performed in vitro experiments, exposing Chinese hamster ovary (CHO) cells to conventional ECT pulses, high-frequency bipolar pulses, and millisecond pulses in the presence of different concentrations of cisplatin. We determined cisplatin uptake by inductively coupled plasma mass spectrometry and cisplatin cytotoxicity by the clonogenic assay. Results We observed that the three tested types of pulses potentiate the uptake and cytotoxicity of cisplatin in an equivalent manner, provided that the electric field is properly adjusted for each pulse type. Furthermore, we quantified that the number of cisplatin molecules, resulting in the eradication of most cells, was 2−7 × 107 per cell. Conclusions High-frequency bipolar pulses and millisecond pulses can potentially be used in ECT to reduce pain and muscle contraction and increase the effect of the immune response in combination with gene electrotransfer, respectively.

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Section: Discussionmentioning

confidence: 99%

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an in vitro study

Scuderi,

Dermol-Cerne,

Scancar

et al. 2024

Radiology and Oncology

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“…Again, similar to the in vivo results, electrochemotherapy with all three chemotherapeutic agents tested induced DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy altered the expression of MHC I, MHC II, PD-L1 and CD40, which was also cell line and chemotherapeutic concentration specific ( 33 ). The data obtained from in vitro and in vivo studies have shown that electrochemotherapy indeed induces immunogenic cell death and is therefore a suitable candidate for combination with ICIs ( 34 ).…”

Section: Electrochemotherapy – Mechanisms Of Actionmentioning

confidence: 99%

Electrochemotherapy combined with immunotherapy – a promising potential in the treatment of cancer

Hadzialjevic,

Omerzel,

Trotovsek

et al. 2024

Front. Immunol.

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Electrochemotherapy is a novel, locoregional therapy that is used to treat cutaneous and deep-seated tumors. The electric pulses used in electrochemotherapy increase the permeability of the cell membranes of the target lesion and thus enhance the delivery of low-permeant cytotoxic drugs to the cells, leading to their death. It has also been postulated that electrochemotherapy acts as an in situ vaccination by inducing immunogenic cell death. This in turn leads to an enhanced systemic antitumor response, which could be further exploited by immunotherapy. However, only a few clinical studies have investigated the role of combined treatment in patients with melanoma, breast cancer, hepatocellular carcinoma, and cutaneous squamous cell carcinoma. In this review, we therefore aim to review the published preclinical evidence on combined treatment and to review clinical studies that have investigated the combined role of electrochemotherapy and immunotherapy.

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“… 8 In contrast, reversible electroporation does not cause cell death but temporarily disrupts the cell membrane in such a way that it becomes permeable for molecules that have hampered transport through the membrane. 9 , 10 , 11 , 12 This phenomenon can be exploited for enhanced drug, DNA or RNA delivery into cells. If we deliver nucleic acids, it is called gene electrotransfer, which can be used for cancer immune-gene therapy; for example, if introduced, DNA or mRNA encodes immunomodulatory molecules.…”

Section: The Use Of Bleomycin Combined With Electroporation (Electroc...mentioning

confidence: 99%

“…This mechanism has been described in radiation therapy, thermal ablative techniques, and electrochemotherapy. 10 , 12 , 19 Several groups have investigated the role of immunogenic cell death in the effectiveness of electrochemotherapy. Now, the experimental data indicate that the response of the tumors varies depending on the immunogenicity of the tumors; more immunogenic tumors respond better to electrochemotherapy than less immunogenic tumors, which was linked to more pronounced immunogenic cell death after electrochemotherapy.…”

Section: Electrochemotherapy Mechanisms Of Actionmentioning

confidence: 99%

“…Now, the experimental data indicate that the response of the tumors varies depending on the immunogenicity of the tumors; more immunogenic tumors respond better to electrochemotherapy than less immunogenic tumors, which was linked to more pronounced immunogenic cell death after electrochemotherapy. 10 , 12 , 20 Additionally, clinical data on the treatment of melanoma demonstrate that local treatment of cutaneous metastases can boost or interact with treatment using immune checkpoint inhibitors, such as pembrolizumab. 21 Patients treated with both electrochemotherapy and immune checkpoint inhibitors had lower disease progression rates and longer survival than those who received pembrolizumab only.…”

Section: Electrochemotherapy Mechanisms Of Actionmentioning

confidence: 99%

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Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An International Network for Sharing Practices on Electrochemotherapy (InspECT) study group report

Muir

Bertino

Groselj

et al. 2023

Radiology and Oncology

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Background Biomedical applications of electroporation are expanding out of the field of oncology into vaccination, treatment of arrhythmias and now in the treatment of vascular malformations. Bleomycin is a widely used sclerosing agent in the treatment of various vascular malformations. The application of electric pulses in addition to bleomycin enhances the effectiveness of the drug, as demonstrated by electrochemotherapy, which utilizes bleomycin in the treatment of tumors. The same principle is used in bleomycin electrosclerotherapy (BEST). The approach seems to be effective in the treatment of low-flow (venous and lymphatic) and, potentially, even high-flow (arteriovenous) malformations. Although there are only a few published reports to date, the surgical community is interested, and an increasing number of centers are applying BEST in the treatment of vascular malformations. Within the International Network for Sharing Practices on Electrochemotherapy (InspECT) consortium, a dedicated working group has been constituted to develop standard operating procedures for BEST and foster clinical trials. Conclusions By treatment standardization and successful completion of clinical trials demonstrating the effectiveness and safety of the approach, higher quality data and better clinical outcomes may be achieved.

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Effects of Electrochemotherapy on Immunologically Important Modifications in Tumor Cells

Cited by 6 publications

References 62 publications

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an in vitro study

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an in vitro study

Electrochemotherapy combined with immunotherapy – a promising potential in the treatment of cancer

Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An International Network for Sharing Practices on Electrochemotherapy (InspECT) study group report

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