Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma

Electrochemotherapy (ECT) is a standard of care in veterinary and human oncology. The treatment induces a well-characterized local immune response which is not able to induce a systemic response. In this retrospective cohort study, we evaluated the addition of gene electrotransfer (GET) of canine IL...

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Main Authors: Matías Tellado, Mariangela De Robertis, Daniela Montagna, Daniela Giovannini, Sergio Salgado, Sebastián Michinski, Emanuela Signori, Felipe Maglietti
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/11/6/1033
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author Matías Tellado
Mariangela De Robertis
Daniela Montagna
Daniela Giovannini
Sergio Salgado
Sebastián Michinski
Emanuela Signori
Felipe Maglietti
author_facet Matías Tellado
Mariangela De Robertis
Daniela Montagna
Daniela Giovannini
Sergio Salgado
Sebastián Michinski
Emanuela Signori
Felipe Maglietti
author_sort Matías Tellado
collection DOAJ
description Electrochemotherapy (ECT) is a standard of care in veterinary and human oncology. The treatment induces a well-characterized local immune response which is not able to induce a systemic response. In this retrospective cohort study, we evaluated the addition of gene electrotransfer (GET) of canine IL-2 peritumorally and IL-12 intramuscularly to enhance the immune response. Thirty canine patients with inoperable oral malignant melanoma were included. Ten patients received ECT+GET as the treatment group, while twenty patients received ECT as the control group. Intravenous bleomycin for the ECT was used in both groups. All patients had compromised lymph nodes which were surgically removed. Plasma levels of interleukins, local response rate, overall survival, and progression-free survival were evaluated. The results show that IL-2 and IL-12 expression peaked around days 7–14 after transfection. Both groups showed similar local response rates and overall survival times. However, progression-free survival resulted significantly better in the ECT+GET group, which is a better indicator than overall survival, as it is not influenced by the criterion used for performing euthanasia. We can conclude that the combination of ECT+GET using IL-2 and IL-12 improves treatment outcomes by slowing down tumoral progression in stage III–IV inoperable canine oral malignant melanoma.
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spelling doaj.art-fb6e0e92a13a4451bd5a3b3a253d5ca62023-11-18T12:58:17ZengMDPI AGVaccines2076-393X2023-05-01116103310.3390/vaccines11061033Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant MelanomaMatías Tellado0Mariangela De Robertis1Daniela Montagna2Daniela Giovannini3Sergio Salgado4Sebastián Michinski5Emanuela Signori6Felipe Maglietti7VetOncologia, Veterinary Oncology Clinic, Buenos Aires 1408, ArgentinaDepartment of Biosciences, Biotechnology and Environment, University of Bari ‘A. Moro’, 70125 Bari, ItalyInstituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires 1425, ArgentinaENEA SSPT-TECS-TEB, Casaccia Research Center, Division of Health Protection Technology (TECS), Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA), 00123 Rome, ItalyCREOVet, Veterinary Oncology Clinic, Lima 04, PeruInstituto de Física Interdsiciplinaria y Aplicada (INFINA), Facultad de Cs Exactas y Naturales, UBA-CONICET, Buenos Aires 1428, ArgentinaLaboratory of Molecular Pathology and Experimental Oncology, Institute of Translational Pharmacology, CNR, Rome 0133, ItalyInstituto Universitario de Ciencias de la Salud, Fundación Barceló—CONICET, Buenos Aires 1117, ArgentinaElectrochemotherapy (ECT) is a standard of care in veterinary and human oncology. The treatment induces a well-characterized local immune response which is not able to induce a systemic response. In this retrospective cohort study, we evaluated the addition of gene electrotransfer (GET) of canine IL-2 peritumorally and IL-12 intramuscularly to enhance the immune response. Thirty canine patients with inoperable oral malignant melanoma were included. Ten patients received ECT+GET as the treatment group, while twenty patients received ECT as the control group. Intravenous bleomycin for the ECT was used in both groups. All patients had compromised lymph nodes which were surgically removed. Plasma levels of interleukins, local response rate, overall survival, and progression-free survival were evaluated. The results show that IL-2 and IL-12 expression peaked around days 7–14 after transfection. Both groups showed similar local response rates and overall survival times. However, progression-free survival resulted significantly better in the ECT+GET group, which is a better indicator than overall survival, as it is not influenced by the criterion used for performing euthanasia. We can conclude that the combination of ECT+GET using IL-2 and IL-12 improves treatment outcomes by slowing down tumoral progression in stage III–IV inoperable canine oral malignant melanoma.https://www.mdpi.com/2076-393X/11/6/1033electroporationelectrogene transferimmune responsecancerdogECT
spellingShingle Matías Tellado
Mariangela De Robertis
Daniela Montagna
Daniela Giovannini
Sergio Salgado
Sebastián Michinski
Emanuela Signori
Felipe Maglietti
Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma
Vaccines
electroporation
electrogene transfer
immune response
cancer
dog
ECT
title Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma
title_full Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma
title_fullStr Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma
title_full_unstemmed Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma
title_short Electrochemotherapy Plus IL-2+IL-12 Gene Electrotransfer in Spontaneous Inoperable Stage III–IV Canine Oral Malignant Melanoma
title_sort electrochemotherapy plus il 2 il 12 gene electrotransfer in spontaneous inoperable stage iii iv canine oral malignant melanoma
topic electroporation
electrogene transfer
immune response
cancer
dog
ECT
url https://www.mdpi.com/2076-393X/11/6/1033
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