Generation of Tumor-activated T cells Using Electroporation. Alinezhadbalalami, N., Graybill, P. M., Imran, K. M., Verbridge, S. S., Allen, I. C., & Davalos, R. V. Bioelectrochemistry, 142:107886, 2021. 1878-562x Alinezhadbalalami, Nastaran Graybill, Philip M Imran, Khan Mohammad Verbridge, Scott S Allen, Irving C Davalos, Rafael V R01 CA213423/CA/NCI NIH HHS/United States R03 AI151494/AI/NIAID NIH HHS/United States R21 EB028429/EB/NIBIB NIH HHS/United States Journal Article Netherlands 2021/07/25 Bioelectrochemistry. 2021 Dec;142:107886. doi: 10.1016/j.bioelechem.2021.107886. Epub 2021 Jul 13.doi abstract bibtex Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. This study introduces a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields. We hypothesize that utilizing high-voltage pulsed electric fields may be an ideal method to activate and expand CTLs due to their non-thermal celldeath mechanism. Tumor cells were subjected to high-frequency irreversible electroporation (HFIRE) with various electric field magnitudes (1250, 2500 V/cm) and pulse widths (1, 5, and 10 µs), or irreversible electroporation (IRE) at 1250 V/cm. The treated tumor cells were subsequently cocultured with CD4+ and CD8+ T cells along with antigen-presenting cells. We show that tumor-activated CTLs can be produced and expanded when exposed to treated tumor cells. Our results suggest that CTLs are more effectively expanded when pulsed with HFIRE conditions that induce significant cell death (longer pulse widths and higher voltages). Activated CD8+ T cells demonstrate cytotoxicity to untreated tumor cells suggesting effector function of the activated CTLs. The activated CTLs produced with our technique could be used for clinical applications with the goal of targeting and eliminating the tumor.
@article{RN117,
author = {Alinezhadbalalami, N. and Graybill, P. M. and Imran, K. M. and Verbridge, S. S. and Allen, I. C. and Davalos, R. V.},
title = {Generation of Tumor-activated T cells Using Electroporation},
journal = {Bioelectrochemistry},
volume = {142},
pages = {107886},
note = {1878-562x
Alinezhadbalalami, Nastaran
Graybill, Philip M
Imran, Khan Mohammad
Verbridge, Scott S
Allen, Irving C
Davalos, Rafael V
R01 CA213423/CA/NCI NIH HHS/United States
R03 AI151494/AI/NIAID NIH HHS/United States
R21 EB028429/EB/NIBIB NIH HHS/United States
Journal Article
Netherlands
2021/07/25
Bioelectrochemistry. 2021 Dec;142:107886. doi: 10.1016/j.bioelechem.2021.107886. Epub 2021 Jul 13.},
abstract = {Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. This study introduces a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields. We hypothesize that utilizing high-voltage pulsed electric fields may be an ideal method to activate and expand CTLs due to their non-thermal celldeath mechanism. Tumor cells were subjected to high-frequency irreversible electroporation (HFIRE) with various electric field magnitudes (1250, 2500 V/cm) and pulse widths (1, 5, and 10 µs), or irreversible electroporation (IRE) at 1250 V/cm. The treated tumor cells were subsequently cocultured with CD4+ and CD8+ T cells along with antigen-presenting cells. We show that tumor-activated CTLs can be produced and expanded when exposed to treated tumor cells. Our results suggest that CTLs are more effectively expanded when pulsed with HFIRE conditions that induce significant cell death (longer pulse widths and higher voltages). Activated CD8+ T cells demonstrate cytotoxicity to untreated tumor cells suggesting effector function of the activated CTLs. The activated CTLs produced with our technique could be used for clinical applications with the goal of targeting and eliminating the tumor.},
keywords = {Cell Line, Tumor
Electroporation/*methods
Glioblastoma/*pathology
Humans
T-Lymphocytes, Cytotoxic/*cytology
Anti-tumor immunity
Antigen presentation
Cytotoxic T cell
High frequency irreversible electroporation
Irreversible electroporation
T cell Activation},
ISSN = {1567-5394 (Print)
1567-5394},
DOI = {10.1016/j.bioelechem.2021.107886},
year = {2021},
type = {Journal Article}
}
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Epub 2021 Jul 13.","abstract":"Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. This study introduces a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields. We hypothesize that utilizing high-voltage pulsed electric fields may be an ideal method to activate and expand CTLs due to their non-thermal celldeath mechanism. Tumor cells were subjected to high-frequency irreversible electroporation (HFIRE) with various electric field magnitudes (1250, 2500 V/cm) and pulse widths (1, 5, and 10 µs), or irreversible electroporation (IRE) at 1250 V/cm. The treated tumor cells were subsequently cocultured with CD4+ and CD8+ T cells along with antigen-presenting cells. We show that tumor-activated CTLs can be produced and expanded when exposed to treated tumor cells. 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V.},\n title = {Generation of Tumor-activated T cells Using Electroporation},\n journal = {Bioelectrochemistry},\n volume = {142},\n pages = {107886},\n note = {1878-562x\nAlinezhadbalalami, Nastaran\nGraybill, Philip M\nImran, Khan Mohammad\nVerbridge, Scott S\nAllen, Irving C\nDavalos, Rafael V\nR01 CA213423/CA/NCI NIH HHS/United States\nR03 AI151494/AI/NIAID NIH HHS/United States\nR21 EB028429/EB/NIBIB NIH HHS/United States\nJournal Article\nNetherlands\n2021/07/25\nBioelectrochemistry. 2021 Dec;142:107886. doi: 10.1016/j.bioelechem.2021.107886. Epub 2021 Jul 13.},\n abstract = {Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. This study introduces a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields. We hypothesize that utilizing high-voltage pulsed electric fields may be an ideal method to activate and expand CTLs due to their non-thermal celldeath mechanism. Tumor cells were subjected to high-frequency irreversible electroporation (HFIRE) with various electric field magnitudes (1250, 2500 V/cm) and pulse widths (1, 5, and 10 µs), or irreversible electroporation (IRE) at 1250 V/cm. The treated tumor cells were subsequently cocultured with CD4+ and CD8+ T cells along with antigen-presenting cells. We show that tumor-activated CTLs can be produced and expanded when exposed to treated tumor cells. Our results suggest that CTLs are more effectively expanded when pulsed with HFIRE conditions that induce significant cell death (longer pulse widths and higher voltages). Activated CD8+ T cells demonstrate cytotoxicity to untreated tumor cells suggesting effector function of the activated CTLs. 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