Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade

DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning...

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Autores principales:	Haoxiao Zuo, Marie-José C. van Lierop, Jorn Kaspers, Remco Bos, Anneke Reurs, Saheli Sarkar, Tania Konry, Alwin Kamermans, Gijs Kooij, Helga E. de Vries, Tanja D. de Gruijl, Alex Karlsson-Parra, Erik H. Manting, Ada M. Kruisbeek, Satwinder Kaur Singh
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	DCP-001 DCOne allogeneic dendritic cell cell-based vaccine acute myeloid leukemia Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/467c11dcb8d4413a8aaeb2c376d6e894
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spelling	oai:doaj.org-article:467c11dcb8d4413a8aaeb2c376d6e8942021-11-25T17:13:08ZTransfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade10.3390/cells101132332073-4409https://doaj.org/article/467c11dcb8d4413a8aaeb2c376d6e8942021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3233https://doaj.org/toc/2073-4409DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activated skin-emigrating DCs. These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies.Haoxiao ZuoMarie-José C. van LieropJorn KaspersRemco BosAnneke ReursSaheli SarkarTania KonryAlwin KamermansGijs KooijHelga E. de VriesTanja D. de GruijlAlex Karlsson-ParraErik H. MantingAda M. KruisbeekSatwinder Kaur SinghMDPI AGarticleDCP-001DCOneallogeneicdendritic cellcell-based vaccineacute myeloid leukemiaBiology (General)QH301-705.5ENCells, Vol 10, Iss 3233, p 3233 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DCP-001 DCOne allogeneic dendritic cell cell-based vaccine acute myeloid leukemia Biology (General) QH301-705.5
spellingShingle	DCP-001 DCOne allogeneic dendritic cell cell-based vaccine acute myeloid leukemia Biology (General) QH301-705.5 Haoxiao Zuo Marie-José C. van Lierop Jorn Kaspers Remco Bos Anneke Reurs Saheli Sarkar Tania Konry Alwin Kamermans Gijs Kooij Helga E. de Vries Tanja D. de Gruijl Alex Karlsson-Parra Erik H. Manting Ada M. Kruisbeek Satwinder Kaur Singh Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
description	DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activated skin-emigrating DCs. These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies.
format	article
author	Haoxiao Zuo Marie-José C. van Lierop Jorn Kaspers Remco Bos Anneke Reurs Saheli Sarkar Tania Konry Alwin Kamermans Gijs Kooij Helga E. de Vries Tanja D. de Gruijl Alex Karlsson-Parra Erik H. Manting Ada M. Kruisbeek Satwinder Kaur Singh
author_facet	Haoxiao Zuo Marie-José C. van Lierop Jorn Kaspers Remco Bos Anneke Reurs Saheli Sarkar Tania Konry Alwin Kamermans Gijs Kooij Helga E. de Vries Tanja D. de Gruijl Alex Karlsson-Parra Erik H. Manting Ada M. Kruisbeek Satwinder Kaur Singh
author_sort	Haoxiao Zuo
title	Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
title_short	Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
title_full	Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
title_fullStr	Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
title_full_unstemmed	Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
title_sort	transfer of cellular content from the allogeneic cell-based cancer vaccine dcp-001 to host dendritic cells hinges on phosphatidylserine and is enhanced by cd47 blockade
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/467c11dcb8d4413a8aaeb2c376d6e894
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Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade

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