Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection

Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-tar...
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Autor*in:	Daniel Delitto [verfasserIn] Daniel J. Zabransky [verfasserIn] Fangluo Chen [verfasserIn] Elizabeth D. Thompson [verfasserIn] Jacquelyn W. Zimmerman [verfasserIn] Todd D. Armstrong [verfasserIn] James M. Leatherman [verfasserIn] Reecha Suri [verfasserIn] Tamara Y. Lopez-Vidal [verfasserIn] Amanda L. Huff [verfasserIn] Melissa R. Lyman [verfasserIn] Samantha R. Guinn [verfasserIn] Marina Baretti [verfasserIn] Luciane T. Kagohara [verfasserIn] Won Jin Ho [verfasserIn] Nilofer S. Azad [verfasserIn] William R. Burns [verfasserIn] Jin He [verfasserIn] Christopher L. Wolfgang [verfasserIn] Richard A. Burkhart [verfasserIn] Lei Zheng [verfasserIn] Mark Yarchoan [verfasserIn] Neeha Zaidi [verfasserIn] Elizabeth M. Jaffee [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery

Übergeordnetes Werk:	In: OncoImmunology - Taylor & Francis Group, 2020, 10(2021), 1
Übergeordnetes Werk:	volume:10 ; year:2021 ; number:1

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1080/2162402X.2021.2001159

Katalog-ID:	DOAJ018984746

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520			\|a Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC.
650		4	\|a pancreatic adenocarcinoma
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700	0		\|a Elizabeth D. Thompson \|e verfasserin \|4 aut
700	0		\|a Jacquelyn W. Zimmerman \|e verfasserin \|4 aut
700	0		\|a Todd D. Armstrong \|e verfasserin \|4 aut
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allfields	10.1080/2162402X.2021.2001159 doi (DE-627)DOAJ018984746 (DE-599)DOAJ97094383247048c2ade5ce77d37edcab DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Daniel Delitto verfasserin aut Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC. pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Daniel J. Zabransky verfasserin aut Fangluo Chen verfasserin aut Elizabeth D. Thompson verfasserin aut Jacquelyn W. Zimmerman verfasserin aut Todd D. Armstrong verfasserin aut James M. Leatherman verfasserin aut Reecha Suri verfasserin aut Tamara Y. Lopez-Vidal verfasserin aut Amanda L. Huff verfasserin aut Melissa R. Lyman verfasserin aut Samantha R. Guinn verfasserin aut Marina Baretti verfasserin aut Luciane T. Kagohara verfasserin aut Won Jin Ho verfasserin aut Nilofer S. Azad verfasserin aut William R. Burns verfasserin aut Jin He verfasserin aut Christopher L. Wolfgang verfasserin aut Richard A. Burkhart verfasserin aut Lei Zheng verfasserin aut Mark Yarchoan verfasserin aut Neeha Zaidi verfasserin aut Elizabeth M. Jaffee verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 10(2021), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:10 year:2021 number:1 https://doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/article/97094383247048c2ade5ce77d37edcab kostenfrei http://dx.doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 1
spelling	10.1080/2162402X.2021.2001159 doi (DE-627)DOAJ018984746 (DE-599)DOAJ97094383247048c2ade5ce77d37edcab DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Daniel Delitto verfasserin aut Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC. pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Daniel J. Zabransky verfasserin aut Fangluo Chen verfasserin aut Elizabeth D. Thompson verfasserin aut Jacquelyn W. Zimmerman verfasserin aut Todd D. Armstrong verfasserin aut James M. Leatherman verfasserin aut Reecha Suri verfasserin aut Tamara Y. Lopez-Vidal verfasserin aut Amanda L. Huff verfasserin aut Melissa R. Lyman verfasserin aut Samantha R. Guinn verfasserin aut Marina Baretti verfasserin aut Luciane T. Kagohara verfasserin aut Won Jin Ho verfasserin aut Nilofer S. Azad verfasserin aut William R. Burns verfasserin aut Jin He verfasserin aut Christopher L. Wolfgang verfasserin aut Richard A. Burkhart verfasserin aut Lei Zheng verfasserin aut Mark Yarchoan verfasserin aut Neeha Zaidi verfasserin aut Elizabeth M. Jaffee verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 10(2021), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:10 year:2021 number:1 https://doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/article/97094383247048c2ade5ce77d37edcab kostenfrei http://dx.doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 1
allfields_unstemmed	10.1080/2162402X.2021.2001159 doi (DE-627)DOAJ018984746 (DE-599)DOAJ97094383247048c2ade5ce77d37edcab DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Daniel Delitto verfasserin aut Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC. pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Daniel J. Zabransky verfasserin aut Fangluo Chen verfasserin aut Elizabeth D. Thompson verfasserin aut Jacquelyn W. Zimmerman verfasserin aut Todd D. Armstrong verfasserin aut James M. Leatherman verfasserin aut Reecha Suri verfasserin aut Tamara Y. Lopez-Vidal verfasserin aut Amanda L. Huff verfasserin aut Melissa R. Lyman verfasserin aut Samantha R. Guinn verfasserin aut Marina Baretti verfasserin aut Luciane T. Kagohara verfasserin aut Won Jin Ho verfasserin aut Nilofer S. Azad verfasserin aut William R. Burns verfasserin aut Jin He verfasserin aut Christopher L. Wolfgang verfasserin aut Richard A. Burkhart verfasserin aut Lei Zheng verfasserin aut Mark Yarchoan verfasserin aut Neeha Zaidi verfasserin aut Elizabeth M. Jaffee verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 10(2021), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:10 year:2021 number:1 https://doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/article/97094383247048c2ade5ce77d37edcab kostenfrei http://dx.doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 1
allfieldsGer	10.1080/2162402X.2021.2001159 doi (DE-627)DOAJ018984746 (DE-599)DOAJ97094383247048c2ade5ce77d37edcab DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Daniel Delitto verfasserin aut Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC. pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Daniel J. Zabransky verfasserin aut Fangluo Chen verfasserin aut Elizabeth D. Thompson verfasserin aut Jacquelyn W. Zimmerman verfasserin aut Todd D. Armstrong verfasserin aut James M. Leatherman verfasserin aut Reecha Suri verfasserin aut Tamara Y. Lopez-Vidal verfasserin aut Amanda L. Huff verfasserin aut Melissa R. Lyman verfasserin aut Samantha R. Guinn verfasserin aut Marina Baretti verfasserin aut Luciane T. Kagohara verfasserin aut Won Jin Ho verfasserin aut Nilofer S. Azad verfasserin aut William R. Burns verfasserin aut Jin He verfasserin aut Christopher L. Wolfgang verfasserin aut Richard A. Burkhart verfasserin aut Lei Zheng verfasserin aut Mark Yarchoan verfasserin aut Neeha Zaidi verfasserin aut Elizabeth M. Jaffee verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 10(2021), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:10 year:2021 number:1 https://doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/article/97094383247048c2ade5ce77d37edcab kostenfrei http://dx.doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 1
allfieldsSound	10.1080/2162402X.2021.2001159 doi (DE-627)DOAJ018984746 (DE-599)DOAJ97094383247048c2ade5ce77d37edcab DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Daniel Delitto verfasserin aut Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC. pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Daniel J. Zabransky verfasserin aut Fangluo Chen verfasserin aut Elizabeth D. Thompson verfasserin aut Jacquelyn W. Zimmerman verfasserin aut Todd D. Armstrong verfasserin aut James M. Leatherman verfasserin aut Reecha Suri verfasserin aut Tamara Y. Lopez-Vidal verfasserin aut Amanda L. Huff verfasserin aut Melissa R. Lyman verfasserin aut Samantha R. Guinn verfasserin aut Marina Baretti verfasserin aut Luciane T. Kagohara verfasserin aut Won Jin Ho verfasserin aut Nilofer S. Azad verfasserin aut William R. Burns verfasserin aut Jin He verfasserin aut Christopher L. Wolfgang verfasserin aut Richard A. Burkhart verfasserin aut Lei Zheng verfasserin aut Mark Yarchoan verfasserin aut Neeha Zaidi verfasserin aut Elizabeth M. Jaffee verfasserin aut In OncoImmunology Taylor & Francis Group, 2020 10(2021), 1 (DE-627)683365428 (DE-600)2645309-5 2162402X nnns volume:10 year:2021 number:1 https://doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/article/97094383247048c2ade5ce77d37edcab kostenfrei http://dx.doi.org/10.1080/2162402X.2021.2001159 kostenfrei https://doaj.org/toc/2162-402X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 1
language	English
source	In OncoImmunology 10(2021), 1 volume:10 year:2021 number:1
sourceStr	In OncoImmunology 10(2021), 1 volume:10 year:2021 number:1
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	OncoImmunology
authorswithroles_txt_mv	Daniel Delitto @@aut@@ Daniel J. Zabransky @@aut@@ Fangluo Chen @@aut@@ Elizabeth D. Thompson @@aut@@ Jacquelyn W. Zimmerman @@aut@@ Todd D. Armstrong @@aut@@ James M. Leatherman @@aut@@ Reecha Suri @@aut@@ Tamara Y. Lopez-Vidal @@aut@@ Amanda L. Huff @@aut@@ Melissa R. Lyman @@aut@@ Samantha R. Guinn @@aut@@ Marina Baretti @@aut@@ Luciane T. Kagohara @@aut@@ Won Jin Ho @@aut@@ Nilofer S. Azad @@aut@@ William R. Burns @@aut@@ Jin He @@aut@@ Christopher L. Wolfgang @@aut@@ Richard A. Burkhart @@aut@@ Lei Zheng @@aut@@ Mark Yarchoan @@aut@@ Neeha Zaidi @@aut@@ Elizabeth M. Jaffee @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	683365428
id	DOAJ018984746
language_de	englisch
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callnumber-first	R - Medicine
author	Daniel Delitto
spellingShingle	Daniel Delitto misc RC581-607 misc RC254-282 misc pancreatic adenocarcinoma misc immunotherapy misc neoantigen misc vaccine misc hydrogel misc surgery misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection
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topic_title	RC581-607 RC254-282 Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection pancreatic adenocarcinoma immunotherapy neoantigen vaccine hydrogel surgery
topic	misc RC581-607 misc RC254-282 misc pancreatic adenocarcinoma misc immunotherapy misc neoantigen misc vaccine misc hydrogel misc surgery misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC581-607 misc RC254-282 misc pancreatic adenocarcinoma misc immunotherapy misc neoantigen misc vaccine misc hydrogel misc surgery misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC581-607 misc RC254-282 misc pancreatic adenocarcinoma misc immunotherapy misc neoantigen misc vaccine misc hydrogel misc surgery misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection
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title_full	Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection
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author_browse	Daniel Delitto Daniel J. Zabransky Fangluo Chen Elizabeth D. Thompson Jacquelyn W. Zimmerman Todd D. Armstrong James M. Leatherman Reecha Suri Tamara Y. Lopez-Vidal Amanda L. Huff Melissa R. Lyman Samantha R. Guinn Marina Baretti Luciane T. Kagohara Won Jin Ho Nilofer S. Azad William R. Burns Jin He Christopher L. Wolfgang Richard A. Burkhart Lei Zheng Mark Yarchoan Neeha Zaidi Elizabeth M. Jaffee
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title_sort	implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection
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title_auth	Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection
abstract	Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC.
abstractGer	Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC.
abstract_unstemmed	Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC.
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title_short	Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection
url	https://doi.org/10.1080/2162402X.2021.2001159 https://doaj.org/article/97094383247048c2ade5ce77d37edcab http://dx.doi.org/10.1080/2162402X.2021.2001159 https://doaj.org/toc/2162-402X
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Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection

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