Electrochemotherapy and immune interactions; A boost to the system?

Bendix, Maura B.; Houston, Aileen; Forde, Patrick F.; Brint, Elizabeth

doi:10.1016/j.ejso.2022.05.023

Cited by 14 publications

(9 citation statements)

References 32 publications

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“…Considerable efforts are also focused on making ECT a systemic treatment by combining it with immunotherapy. 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.…”

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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“…It enables targeted delivery of anticancer drugs to cells exposed to electric pulses, which makes them more effective at lower doses [ 2 ]. The capacity of electrochemotherapy to induce ICD mainly depends on the chemotherapeutic used but also on the treated tumor type [ 32 , 46 ]. During ICD, dying tumor cells release DAMPs that stimulate an adaptive immune response against tumor neo-antigens, thus turning them into an anticancer vaccine [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…The capacity of electrochemotherapy to induce ICD mainly depends on the chemotherapeutic used but also on the treated tumor type [ 32 , 46 ]. During ICD, dying tumor cells release DAMPs that stimulate an adaptive immune response against tumor neo-antigens, thus turning them into an anticancer vaccine [ 46 ]. In this study, we evaluated the potential of electrochemotherapy with the clinically relevant chemotherapeutics CDDP, OXA and BLM to induce ICD-associated DAMPs and to cause changes in the expression of other immunologically important cellular markers in tumor cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Effects of Electrochemotherapy on Immunologically Important Modifications in Tumor Cells

et al. 2023

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Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.

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“…Nevertheless, a clear mechanism of these effects is unknown, showing the need of more systemic investigations. Possible directions can be drawn from very recent reviews on interaction of EP-based therapies and immune response [ 45 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Ruzgys

Navickaitė

Palepšienė

et al. 2022

Cancers

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Electroporation-based antitumor therapies, including bleomycin electrotransfer, calcium electroporation, and irreversible electroporation, are very effective on directly treated tumors, but have no or low effect on distal nodules. In this study, we aimed to investigate the abscopal effect following calcium electroporation and bleomycin electrotransfer and to find out the effect of the increase of IL-2 serum concentration by muscle transfection. The bystander effect was analyzed in in vitro studies on 4T1tumor cells, while abscopal effect was investigated in an in vivo setting using Balb/c mice bearing 4T1 tumors. ELISA was used to monitor IL-2 serum concentration. We showed that, similarly to cell treatment with bleomycin electrotransfer, the bystander effect occurs also following calcium electroporation and that these effects can be combined. Combination of these treatments also resulted in the enhancement of the abscopal effect in vivo. Since these treatments resulted in an increase of IL-2 serum concentration only in mice bearing one but not two tumors, we increased IL-2 serum concentration by muscle transfection. Although this did not enhance the abscopal effect of combined tumor treatment using calcium electroporation and bleomycin electrotransfer, boosting of IL-2 serum concentration had a significant inhibitory effect on directly treated tumors.

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Electrochemotherapy and immune interactions; A boost to the system?

Cited by 14 publications

References 32 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

Effects of Electrochemotherapy on Immunologically Important Modifications in Tumor Cells

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

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