Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer

Abstract T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival...

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Autores principales:	Janos L. Tanyi, Cheryl L.-L. Chiang, Johanna Chiffelle, Anne-Christine Thierry, Petra Baumgartener, Florian Huber, Christine Goepfert, David Tarussio, Stephanie Tissot, Drew A. Torigian, Harvey L. Nisenbaum, Brian J. Stevenson, Hajer Fritah Guiren, Ritaparna Ahmed, Anne-Laure Huguenin-Bergenat, Emese Zsiros, Michal Bassani-Sternberg, Rosemarie Mick, Daniel J. Powell, George Coukos, Alexandre Harari, Lana E. Kandalaft
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ba1d3a5199c64080b68ad63708532dda
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spelling	oai:doaj.org-article:ba1d3a5199c64080b68ad63708532dda2021-12-02T13:17:48ZPersonalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer10.1038/s41541-021-00297-52059-0105https://doaj.org/article/ba1d3a5199c64080b68ad63708532dda2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00297-5https://doaj.org/toc/2059-0105Abstract T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients’ prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8+ T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.Janos L. TanyiCheryl L.-L. ChiangJohanna ChiffelleAnne-Christine ThierryPetra BaumgartenerFlorian HuberChristine GoepfertDavid TarussioStephanie TissotDrew A. TorigianHarvey L. NisenbaumBrian J. StevensonHajer Fritah GuirenRitaparna AhmedAnne-Laure Huguenin-BergenatEmese ZsirosMichal Bassani-SternbergRosemarie MickDaniel J. PowellGeorge CoukosAlexandre HarariLana E. KandalaftNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Janos L. Tanyi Cheryl L.-L. Chiang Johanna Chiffelle Anne-Christine Thierry Petra Baumgartener Florian Huber Christine Goepfert David Tarussio Stephanie Tissot Drew A. Torigian Harvey L. Nisenbaum Brian J. Stevenson Hajer Fritah Guiren Ritaparna Ahmed Anne-Laure Huguenin-Bergenat Emese Zsiros Michal Bassani-Sternberg Rosemarie Mick Daniel J. Powell George Coukos Alexandre Harari Lana E. Kandalaft Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
description	Abstract T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients’ prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8+ T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.
format	article
author	Janos L. Tanyi Cheryl L.-L. Chiang Johanna Chiffelle Anne-Christine Thierry Petra Baumgartener Florian Huber Christine Goepfert David Tarussio Stephanie Tissot Drew A. Torigian Harvey L. Nisenbaum Brian J. Stevenson Hajer Fritah Guiren Ritaparna Ahmed Anne-Laure Huguenin-Bergenat Emese Zsiros Michal Bassani-Sternberg Rosemarie Mick Daniel J. Powell George Coukos Alexandre Harari Lana E. Kandalaft
author_facet	Janos L. Tanyi Cheryl L.-L. Chiang Johanna Chiffelle Anne-Christine Thierry Petra Baumgartener Florian Huber Christine Goepfert David Tarussio Stephanie Tissot Drew A. Torigian Harvey L. Nisenbaum Brian J. Stevenson Hajer Fritah Guiren Ritaparna Ahmed Anne-Laure Huguenin-Bergenat Emese Zsiros Michal Bassani-Sternberg Rosemarie Mick Daniel J. Powell George Coukos Alexandre Harari Lana E. Kandalaft
author_sort	Janos L. Tanyi
title	Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
title_short	Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
title_full	Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
title_fullStr	Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
title_full_unstemmed	Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer
title_sort	personalized cancer vaccine strategy elicits polyfunctional t cells and demonstrates clinical benefits in ovarian cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ba1d3a5199c64080b68ad63708532dda
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Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer

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