High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas. Campelo, S. N., Lorenzo, M. F., Partridge, B., Alinezhadbalalami, N., Kani, Y., Garcia, J., Saunier, S., Thomas, S. C., Hinckley, J., Verbridge, S. S., Davalos, R. V., & Rossmeisl, J. H. Front Oncol, 13:1171278, 2023. 2234-943x Campelo, Sabrina N Lorenzo, Melvin F Partridge, Brittanie Alinezhadbalalami, Nastaran Kani, Yukitaka Garcia, Josefa Saunier, Sofie Thomas, Sean C Hinckley, Jonathan Verbridge, Scott S Davalos, Rafael V Rossmeisl, John H Jr P01 CA207206/CA/NCI NIH HHS/United States Journal Article Switzerland 2023/05/22 Front Oncol. 2023 May 5;13:1171278. doi: 10.3389/fonc.2023.1171278. eCollection 2023.doi abstract bibtex BACKGROUND: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas. METHODS: Hydrogel tissue scaffolds and numerical modeling were used to inform in-vivo H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model. Fischer rats were separated into five treatment cohorts including high-dose H-FIRE (1750V/cm), low-dose H-FIRE (600V/cm), combinatorial high-dose H-FIRE + liposomal doxorubicin, low-dose H-FIRE + liposomal doxorubicin, and standalone liposomal doxorubicin groups. Cohorts were compared against a standalone tumor-bearing sham group which received no therapeutic intervention. To further enhance the translational value of our work, we characterize the local and systemic immune responses to intracranial H-FIRE at the study timepoint. RESULTS: The median survival for each cohort are as follows: 31 days (high-dose H-FIRE), 38 days (low-dose H-FIRE), 37.5 days (high-dose H-FIRE + liposomal doxorubicin), 27 days (low-dose H-FIRE + liposomal doxorubicin), 20 days (liposomal doxorubicin), and 26 days (sham). A statistically greater overall survival fraction was noted in the high-dose H-FIRE + liposomal doxorubicin (50%, p = 0.044), high-dose H-FIRE (28.6%, p = 0.034), and the low-dose H-FIRE (20%, p = 0.0214) compared to the sham control (0%). Compared to sham controls, brain sections of rats treated with H-FIRE demonstrated significant increases in IHC scores for CD3+ T-cells (p = 0.0014), CD79a+ B-cells (p = 0.01), IBA-1+ dendritic cells/microglia (p = 0.04), CD8+ cytotoxic T-cells (p = 0.0004), and CD86+ M1 macrophages (p = 0.01). CONCLUSIONS: H-FIRE may be used as both a monotherapy and a combinatorial therapy to improve survival in the treatment of malignant gliomas while also promoting the presence of infiltrative immune cells.
@article{RN94,
author = {Campelo, S. N. and Lorenzo, M. F. and Partridge, B. and Alinezhadbalalami, N. and Kani, Y. and Garcia, J. and Saunier, S. and Thomas, S. C. and Hinckley, J. and Verbridge, S. S. and Davalos, R. V. and Rossmeisl, J. H., Jr.},
title = {High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas},
journal = {Front Oncol},
volume = {13},
pages = {1171278},
note = {2234-943x
Campelo, Sabrina N
Lorenzo, Melvin F
Partridge, Brittanie
Alinezhadbalalami, Nastaran
Kani, Yukitaka
Garcia, Josefa
Saunier, Sofie
Thomas, Sean C
Hinckley, Jonathan
Verbridge, Scott S
Davalos, Rafael V
Rossmeisl, John H Jr
P01 CA207206/CA/NCI NIH HHS/United States
Journal Article
Switzerland
2023/05/22
Front Oncol. 2023 May 5;13:1171278. doi: 10.3389/fonc.2023.1171278. eCollection 2023.},
abstract = {BACKGROUND: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas. METHODS: Hydrogel tissue scaffolds and numerical modeling were used to inform in-vivo H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model. Fischer rats were separated into five treatment cohorts including high-dose H-FIRE (1750V/cm), low-dose H-FIRE (600V/cm), combinatorial high-dose H-FIRE + liposomal doxorubicin, low-dose H-FIRE + liposomal doxorubicin, and standalone liposomal doxorubicin groups. Cohorts were compared against a standalone tumor-bearing sham group which received no therapeutic intervention. To further enhance the translational value of our work, we characterize the local and systemic immune responses to intracranial H-FIRE at the study timepoint. RESULTS: The median survival for each cohort are as follows: 31 days (high-dose H-FIRE), 38 days (low-dose H-FIRE), 37.5 days (high-dose H-FIRE + liposomal doxorubicin), 27 days (low-dose H-FIRE + liposomal doxorubicin), 20 days (liposomal doxorubicin), and 26 days (sham). A statistically greater overall survival fraction was noted in the high-dose H-FIRE + liposomal doxorubicin (50%, p = 0.044), high-dose H-FIRE (28.6%, p = 0.034), and the low-dose H-FIRE (20%, p = 0.0214) compared to the sham control (0%). Compared to sham controls, brain sections of rats treated with H-FIRE demonstrated significant increases in IHC scores for CD3+ T-cells (p = 0.0014), CD79a+ B-cells (p = 0.01), IBA-1+ dendritic cells/microglia (p = 0.04), CD8+ cytotoxic T-cells (p = 0.0004), and CD86+ M1 macrophages (p = 0.01). CONCLUSIONS: H-FIRE may be used as both a monotherapy and a combinatorial therapy to improve survival in the treatment of malignant gliomas while also promoting the presence of infiltrative immune cells.},
keywords = {blood-brain barrier disruption
electroporation
glioblastoma
immune response
intracranial
numerical modeling
pulsed electric field (PEF)},
ISSN = {2234-943X (Print)
2234-943x},
DOI = {10.3389/fonc.2023.1171278},
year = {2023},
type = {Journal Article}
}
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H."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Campelo"],"firstnames":["S.","N."],"suffixes":[]},{"propositions":[],"lastnames":["Lorenzo"],"firstnames":["M.","F."],"suffixes":[]},{"propositions":[],"lastnames":["Partridge"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Alinezhadbalalami"],"firstnames":["N."],"suffixes":[]},{"propositions":[],"lastnames":["Kani"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Garcia"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Saunier"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Thomas"],"firstnames":["S.","C."],"suffixes":[]},{"propositions":[],"lastnames":["Hinckley"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Verbridge"],"firstnames":["S.","S."],"suffixes":[]},{"propositions":[],"lastnames":["Davalos"],"firstnames":["R.","V."],"suffixes":[]},{"propositions":[],"lastnames":["Rossmeisl"],"firstnames":["J.","H."],"suffixes":["Jr."]}],"title":"High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas","journal":"Front Oncol","volume":"13","pages":"1171278","note":"2234-943x Campelo, Sabrina N Lorenzo, Melvin F Partridge, Brittanie Alinezhadbalalami, Nastaran Kani, Yukitaka Garcia, Josefa Saunier, Sofie Thomas, Sean C Hinckley, Jonathan Verbridge, Scott S Davalos, Rafael V Rossmeisl, John H Jr P01 CA207206/CA/NCI NIH HHS/United States Journal Article Switzerland 2023/05/22 Front Oncol. 2023 May 5;13:1171278. doi: 10.3389/fonc.2023.1171278. eCollection 2023.","abstract":"BACKGROUND: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas. METHODS: Hydrogel tissue scaffolds and numerical modeling were used to inform in-vivo H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model. Fischer rats were separated into five treatment cohorts including high-dose H-FIRE (1750V/cm), low-dose H-FIRE (600V/cm), combinatorial high-dose H-FIRE + liposomal doxorubicin, low-dose H-FIRE + liposomal doxorubicin, and standalone liposomal doxorubicin groups. Cohorts were compared against a standalone tumor-bearing sham group which received no therapeutic intervention. To further enhance the translational value of our work, we characterize the local and systemic immune responses to intracranial H-FIRE at the study timepoint. RESULTS: The median survival for each cohort are as follows: 31 days (high-dose H-FIRE), 38 days (low-dose H-FIRE), 37.5 days (high-dose H-FIRE + liposomal doxorubicin), 27 days (low-dose H-FIRE + liposomal doxorubicin), 20 days (liposomal doxorubicin), and 26 days (sham). A statistically greater overall survival fraction was noted in the high-dose H-FIRE + liposomal doxorubicin (50%, p = 0.044), high-dose H-FIRE (28.6%, p = 0.034), and the low-dose H-FIRE (20%, p = 0.0214) compared to the sham control (0%). Compared to sham controls, brain sections of rats treated with H-FIRE demonstrated significant increases in IHC scores for CD3+ T-cells (p = 0.0014), CD79a+ B-cells (p = 0.01), IBA-1+ dendritic cells/microglia (p = 0.04), CD8+ cytotoxic T-cells (p = 0.0004), and CD86+ M1 macrophages (p = 0.01). CONCLUSIONS: H-FIRE may be used as both a monotherapy and a combinatorial therapy to improve survival in the treatment of malignant gliomas while also promoting the presence of infiltrative immune cells.","keywords":"blood-brain barrier disruption electroporation glioblastoma immune response intracranial numerical modeling pulsed electric field (PEF)","issn":"2234-943X (Print) 2234-943x","doi":"10.3389/fonc.2023.1171278","year":"2023","bibtex":"@article{RN94,\n author = {Campelo, S. N. and Lorenzo, M. F. and Partridge, B. and Alinezhadbalalami, N. and Kani, Y. and Garcia, J. and Saunier, S. and Thomas, S. C. and Hinckley, J. and Verbridge, S. S. and Davalos, R. V. and Rossmeisl, J. H., Jr.},\n title = {High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas},\n journal = {Front Oncol},\n volume = {13},\n pages = {1171278},\n note = {2234-943x\nCampelo, Sabrina N\nLorenzo, Melvin F\nPartridge, Brittanie\nAlinezhadbalalami, Nastaran\nKani, Yukitaka\nGarcia, Josefa\nSaunier, Sofie\nThomas, Sean C\nHinckley, Jonathan\nVerbridge, Scott S\nDavalos, Rafael V\nRossmeisl, John H Jr\nP01 CA207206/CA/NCI NIH HHS/United States\nJournal Article\nSwitzerland\n2023/05/22\nFront Oncol. 2023 May 5;13:1171278. doi: 10.3389/fonc.2023.1171278. eCollection 2023.},\n abstract = {BACKGROUND: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas. METHODS: Hydrogel tissue scaffolds and numerical modeling were used to inform in-vivo H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model. Fischer rats were separated into five treatment cohorts including high-dose H-FIRE (1750V/cm), low-dose H-FIRE (600V/cm), combinatorial high-dose H-FIRE + liposomal doxorubicin, low-dose H-FIRE + liposomal doxorubicin, and standalone liposomal doxorubicin groups. Cohorts were compared against a standalone tumor-bearing sham group which received no therapeutic intervention. To further enhance the translational value of our work, we characterize the local and systemic immune responses to intracranial H-FIRE at the study timepoint. RESULTS: The median survival for each cohort are as follows: 31 days (high-dose H-FIRE), 38 days (low-dose H-FIRE), 37.5 days (high-dose H-FIRE + liposomal doxorubicin), 27 days (low-dose H-FIRE + liposomal doxorubicin), 20 days (liposomal doxorubicin), and 26 days (sham). A statistically greater overall survival fraction was noted in the high-dose H-FIRE + liposomal doxorubicin (50%, p = 0.044), high-dose H-FIRE (28.6%, p = 0.034), and the low-dose H-FIRE (20%, p = 0.0214) compared to the sham control (0%). Compared to sham controls, brain sections of rats treated with H-FIRE demonstrated significant increases in IHC scores for CD3+ T-cells (p = 0.0014), CD79a+ B-cells (p = 0.01), IBA-1+ dendritic cells/microglia (p = 0.04), CD8+ cytotoxic T-cells (p = 0.0004), and CD86+ M1 macrophages (p = 0.01). 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