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Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors
BACKGROUND: Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243723/ https://www.ncbi.nlm.nih.gov/pubmed/34187428 http://dx.doi.org/10.1186/s12885-021-08522-z |
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author | Innamarato, Patrick Morse, Jennifer Mackay, Amy Asby, Sarah Beatty, Matthew Blauvelt, Jamie Kidd, Scott Mullinax, John E. Sarnaik, Amod A. Pilon-Thomas, Shari |
author_facet | Innamarato, Patrick Morse, Jennifer Mackay, Amy Asby, Sarah Beatty, Matthew Blauvelt, Jamie Kidd, Scott Mullinax, John E. Sarnaik, Amod A. Pilon-Thomas, Shari |
author_sort | Innamarato, Patrick |
collection | PubMed |
description | BACKGROUND: Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients. METHODS: In this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA). RESULTS: In this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11b(+)Gr-1(+) cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α. CONCLUSIONS: These results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer. |
format | Online Article Text |
id | pubmed-8243723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82437232021-06-30 Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors Innamarato, Patrick Morse, Jennifer Mackay, Amy Asby, Sarah Beatty, Matthew Blauvelt, Jamie Kidd, Scott Mullinax, John E. Sarnaik, Amod A. Pilon-Thomas, Shari BMC Cancer Research BACKGROUND: Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients. METHODS: In this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA). RESULTS: In this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11b(+)Gr-1(+) cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α. CONCLUSIONS: These results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer. BioMed Central 2021-06-30 /pmc/articles/PMC8243723/ /pubmed/34187428 http://dx.doi.org/10.1186/s12885-021-08522-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Innamarato, Patrick Morse, Jennifer Mackay, Amy Asby, Sarah Beatty, Matthew Blauvelt, Jamie Kidd, Scott Mullinax, John E. Sarnaik, Amod A. Pilon-Thomas, Shari Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
title | Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
title_full | Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
title_fullStr | Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
title_full_unstemmed | Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
title_short | Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
title_sort | intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243723/ https://www.ncbi.nlm.nih.gov/pubmed/34187428 http://dx.doi.org/10.1186/s12885-021-08522-z |
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