Periodic Reporting for period 1 - PlasmACT (Plasma Medicine against Actinic Keratosis)
Periodo di rendicontazione: 2024-01-01 al 2025-12-31
Physical technologies are playing an increasing role in medicine; among these, cold (gas) plasma – partially ionized gas generated at near‑body temperature – shows promise, especially in dermatology. Based on positive clinical results in wound care and encouraging preclinical cancer data, the plasmACT network investigates cold‑plasma treatment for actinic keratosis (AK), a highly prevalent, sun‑induced precancerous condition (affecting ~50% of older white males in Europe) that can progress to squamous‑cell carcinoma. Current AK therapies have limited efficacy, side effects, and cost burdens; early clinical evidence indicates cold plasma can induce lesion regression with few side effects. PlasmACT unites experts across physics, engineering, chemistry, biology, medicine, regulation, and industry to advance a scalable MultiJet device (GREMI) that treats larger, uneven areas more efficiently than single‑jet systems. The project will develop the device from lab prototype to clinical candidate by characterizing its physical, chemical, and biological effects across in vitro, ex vivo, and in vivo models.
Key objectives of the plasmACT consortium are: refine MultiJet plasma physics; ensure regulatory‑aware device design; map reactive‑species generation (experiments + modelling); define electric‑field and plasma–tissue effects; elucidate keratinocyte biochemistry and immunological responses; and enable technology transfer and commercialization. The overall aim is a safe, cost‑effective plasma therapy for early AK treatment and strengthened European leadership in plasma medicine.
Key objectives of the plasmACT consortium are: refine MultiJet plasma physics; ensure regulatory‑aware device design; map reactive‑species generation (experiments + modelling); define electric‑field and plasma–tissue effects; elucidate keratinocyte biochemistry and immunological responses; and enable technology transfer and commercialization. The overall aim is a safe, cost‑effective plasma therapy for early AK treatment and strengthened European leadership in plasma medicine.
Implementation:
- successful project implementation and candidate recruitment (2024), with all eight PhD positions occupied by fall 2024 at five different consortium members (GREMI Orleans, University of Antwerpen, University of Eindhoven, University Medicine Rostock, INP Greifswald)
- delivery of five identical laboratory-level cold plasma devices (MultiJet) to the consortium members by the GREMI Orleans (fall 2024), ensuring comparable and reproducible experiments in the plasmACT project
Research:
- physico-chemical characteristics of the MultiJet device determined, including temperature and electrical field profile, discharge morphology, and reactive species generation
- two different computational models (0D and 2D fluid model) were established to predict the behaviour and formation of reactive species of the discharge, facilitating the design of biomedical experiments and allowing mechanistic understanding
- membrane poration models show increased permeability, supported by a computational model on skin permittivity for reactive oxygen species, comparing healthy skin and AK lesion skin
- MultiJet device passed OECD Test 487 (Test for mutagenicity) – no mutagenicity detected
- in vitro models using three different cell lines (normal, cancerous, AK phenotype) revealed an impact of the MultiJet on:
a) Cellular lipid profiles, showing stress response signals (abundance changes in various lipid classes)
b) Cellular protein expression pattern, e.g. induction of several anti-oxidant defence pathways
c) Cell origin-dependent decrease in viability (cancerous > AK phenotype >> normal), accompanied by a corresponding increase in free intracellular reactive oxygen species
d) Cell origin-dependent secretion of immunomodulatory cytokines, with strong signals for immune cell recruiting from cancerous and AK phenotype cell models, contributing to increased phagocytosis
e) Secretion of damage-associated molecular pattern release by diseased skin cells, indicative for immunogenic cell death induction
- in vivo rodent model study of ultraviolet light exposure-induced AK successfully established
In progress/future work:
- elucidate lipid and protein oxidation, supported by advanced computational models predicting kinetic rates
- elucidating the crosstalk between lipid and protein oxidation
- above state-of-the-art computational homology model on protein-protein crosstalk after MultiJet exposure, contributing to molecular-level understanding of in vivo biomedical effects
- in-depth analysis of immunomodulatory effects of the MultiJet using co-culture and ex vivo models
- exploitation of an in vivo AK rodent model (sample collection for subsequent consortium-wide multi-omics analysis in progress)
- further promotion of MultiJet device to comply with medical product guidelines, including electrical safety and patient impact
education, dissemination, outreach:
- annual kick-off/status seminars bringing together all doctoral candidates (DCs), Principal Investigators, and industry partners
- successful implementation of bi-annual dedicated schools and seminars with high-profile scientific and soft-skill lectures for plasmACT PhD students (open to adjacent audience/students)
- visibility of the project and selected achievements in the web (https://plasmact.eu/(si apre in una nuova finestra)) and on social media (LinkedIn: plasmACT, Instagram @plasmact_eu) managed by the doctoral candidates
- successful participation of all doctoral candidates in at least one international workshop or conference (oral/poster presentation), including GDR HappyBio Paris 2024, ADF Berlin 2025, PlasTHER meeting Barcelona 2025
- two DC first-author publications in high-ranked peer-reviewed journals, and further eight manuscripts in preparation
- successful project implementation and candidate recruitment (2024), with all eight PhD positions occupied by fall 2024 at five different consortium members (GREMI Orleans, University of Antwerpen, University of Eindhoven, University Medicine Rostock, INP Greifswald)
- delivery of five identical laboratory-level cold plasma devices (MultiJet) to the consortium members by the GREMI Orleans (fall 2024), ensuring comparable and reproducible experiments in the plasmACT project
Research:
- physico-chemical characteristics of the MultiJet device determined, including temperature and electrical field profile, discharge morphology, and reactive species generation
- two different computational models (0D and 2D fluid model) were established to predict the behaviour and formation of reactive species of the discharge, facilitating the design of biomedical experiments and allowing mechanistic understanding
- membrane poration models show increased permeability, supported by a computational model on skin permittivity for reactive oxygen species, comparing healthy skin and AK lesion skin
- MultiJet device passed OECD Test 487 (Test for mutagenicity) – no mutagenicity detected
- in vitro models using three different cell lines (normal, cancerous, AK phenotype) revealed an impact of the MultiJet on:
a) Cellular lipid profiles, showing stress response signals (abundance changes in various lipid classes)
b) Cellular protein expression pattern, e.g. induction of several anti-oxidant defence pathways
c) Cell origin-dependent decrease in viability (cancerous > AK phenotype >> normal), accompanied by a corresponding increase in free intracellular reactive oxygen species
d) Cell origin-dependent secretion of immunomodulatory cytokines, with strong signals for immune cell recruiting from cancerous and AK phenotype cell models, contributing to increased phagocytosis
e) Secretion of damage-associated molecular pattern release by diseased skin cells, indicative for immunogenic cell death induction
- in vivo rodent model study of ultraviolet light exposure-induced AK successfully established
In progress/future work:
- elucidate lipid and protein oxidation, supported by advanced computational models predicting kinetic rates
- elucidating the crosstalk between lipid and protein oxidation
- above state-of-the-art computational homology model on protein-protein crosstalk after MultiJet exposure, contributing to molecular-level understanding of in vivo biomedical effects
- in-depth analysis of immunomodulatory effects of the MultiJet using co-culture and ex vivo models
- exploitation of an in vivo AK rodent model (sample collection for subsequent consortium-wide multi-omics analysis in progress)
- further promotion of MultiJet device to comply with medical product guidelines, including electrical safety and patient impact
education, dissemination, outreach:
- annual kick-off/status seminars bringing together all doctoral candidates (DCs), Principal Investigators, and industry partners
- successful implementation of bi-annual dedicated schools and seminars with high-profile scientific and soft-skill lectures for plasmACT PhD students (open to adjacent audience/students)
- visibility of the project and selected achievements in the web (https://plasmact.eu/(si apre in una nuova finestra)) and on social media (LinkedIn: plasmACT, Instagram @plasmact_eu) managed by the doctoral candidates
- successful participation of all doctoral candidates in at least one international workshop or conference (oral/poster presentation), including GDR HappyBio Paris 2024, ADF Berlin 2025, PlasTHER meeting Barcelona 2025
- two DC first-author publications in high-ranked peer-reviewed journals, and further eight manuscripts in preparation
- a new, multiple jet-configured non-thermal atmospheric pressure plasma source, designed to be used for biomedical applications, has been built and distributed to all beneficiaries of the action (November 2024), comprising an advanced design, device prototype in accordance with medical products legislation (subject to further testing during project lifetime)
- The accumulation of physical, chemical, and biomedical data into a single pool supported by advanced computational models on a single cold plasma device was achieved, ensuring safety and efficacy
- immunostimulatory activity on cancer/AK phenotype cells surpassing impact on normal cells, suggesting the relevance of cold plasma/MultiJet for future clinical application
- The accumulation of physical, chemical, and biomedical data into a single pool supported by advanced computational models on a single cold plasma device was achieved, ensuring safety and efficacy
- immunostimulatory activity on cancer/AK phenotype cells surpassing impact on normal cells, suggesting the relevance of cold plasma/MultiJet for future clinical application