Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting

Matthew M Seavey, Yvonne PatersonDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Targeting tumors using cancer vaccine therapeutics has several advantages including the induction of long-term immunity, prime boost strategies for additional tr...

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Autores principales:	Matthew M Seavey, Yvonne Paterson
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e31ca0e3c7a741ccbd52298d2cf2eba4
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spelling	oai:doaj.org-article:e31ca0e3c7a741ccbd52298d2cf2eba42021-12-02T02:47:57ZAntiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting1179-1314https://doaj.org/article/e31ca0e3c7a741ccbd52298d2cf2eba42009-10-01T00:00:00Zhttp://www.dovepress.com/antiangiogenesis-immunotherapy-induces-epitope-spreading-to-her-2neu-r-a3606https://doaj.org/toc/1179-1314Matthew M Seavey, Yvonne PatersonDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Targeting tumors using cancer vaccine therapeutics has several advantages including the induction of long-term immunity, prime boost strategies for additional treatments and reduced side effects compared to conventional chemotherapeutics. However, one problem in targeting tumor antigens directly is that this can lead to antigen loss or immunoediting. We hypothesized that directing the immune response to a normal cell type required for tumor growth and survival could provide a more stable immunotherapeutic target. We thus examined the ability of an antiangiogenesis, Listeria monocytogenes (Lm)-based vector to deliver extracellular and intracellular fragments of the mouse vascular endothelial growth factor receptor-2/Flk-1 molecule, Lm-LLO-Flk-E1, and Lm-LLO-Flk-11 respectively, in an autochthonous model for Her-2/neu+ breast cancer. We found that these vaccines could cause epitope spreading to the endogenous tumor protein Her-2/neu and significantly delay tumor onset. However, tumors that grew out overtime accumulated mutations in the Her-2/neu molecule near or within cytotoxic T lymphocytes epitopes. We show here for the first time how an antiangiogenesis immunotherapy can be used to delay the onset of a spontaneous tumor through epitope spreading and determine a possible mechanism of how immunoediting of an endogenous tumor protein can allow for tumor escape and outgrowth in an autochthonous mouse model for Her-2/neu+ breast cancer.Keywords: Listeria, Her-2/neu, immunotherapy, antiangiogenesis, immunoediting Matthew M SeaveyYvonne PatersonDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2009, Iss default, Pp 19-30 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Matthew M Seavey Yvonne Paterson Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting
description	Matthew M Seavey, Yvonne PatersonDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Targeting tumors using cancer vaccine therapeutics has several advantages including the induction of long-term immunity, prime boost strategies for additional treatments and reduced side effects compared to conventional chemotherapeutics. However, one problem in targeting tumor antigens directly is that this can lead to antigen loss or immunoediting. We hypothesized that directing the immune response to a normal cell type required for tumor growth and survival could provide a more stable immunotherapeutic target. We thus examined the ability of an antiangiogenesis, Listeria monocytogenes (Lm)-based vector to deliver extracellular and intracellular fragments of the mouse vascular endothelial growth factor receptor-2/Flk-1 molecule, Lm-LLO-Flk-E1, and Lm-LLO-Flk-11 respectively, in an autochthonous model for Her-2/neu+ breast cancer. We found that these vaccines could cause epitope spreading to the endogenous tumor protein Her-2/neu and significantly delay tumor onset. However, tumors that grew out overtime accumulated mutations in the Her-2/neu molecule near or within cytotoxic T lymphocytes epitopes. We show here for the first time how an antiangiogenesis immunotherapy can be used to delay the onset of a spontaneous tumor through epitope spreading and determine a possible mechanism of how immunoediting of an endogenous tumor protein can allow for tumor escape and outgrowth in an autochthonous mouse model for Her-2/neu+ breast cancer.Keywords: Listeria, Her-2/neu, immunotherapy, antiangiogenesis, immunoediting
format	article
author	Matthew M Seavey Yvonne Paterson
author_facet	Matthew M Seavey Yvonne Paterson
author_sort	Matthew M Seavey
title	Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting
title_short	Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting
title_full	Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting
title_fullStr	Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting
title_full_unstemmed	Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting
title_sort	antiangiogenesis immunotherapy induces epitope spreading to her-2/neu resulting in breast tumor immunoediting
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/e31ca0e3c7a741ccbd52298d2cf2eba4
work_keys_str_mv	AT matthewmseavey antiangiogenesisimmunotherapyinducesepitopespreadingtoher2neuresultinginbreasttumorimmunoediting AT yvonnepaterson antiangiogenesisimmunotherapyinducesepitopespreadingtoher2neuresultinginbreasttumorimmunoediting
_version_	1718402194433114112

Antiangiogenesis immunotherapy induces epitope spreading to Her-2/neu resulting in breast tumor immunoediting

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