Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens

Abstract Adoptive T-cell transfer (ACT) offers a curative therapeutic option for subsets of melanoma and hematological cancer patients. To increase response rates and broaden the applicability of ACT, it is necessary to improve the post-infusion performance of the transferred T cells. The design of...

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Autores principales:	Ditte E. Jæhger, Mie L. Hübbe, Martin K. Kræmer, Gael Clergeaud, André V. Olsen, Camilla Stavnsbjerg, Mette N. Wiinholt, Andreas Kjær, Jonas R. Henriksen, Anders E. Hansen, Thomas L. Andresen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a35c9f9e5f3d461484acacf388c2f25e
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spelling	oai:doaj.org-article:a35c9f9e5f3d461484acacf388c2f25e2021-12-02T18:01:48ZEnhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens10.1038/s41598-021-99347-02045-2322https://doaj.org/article/a35c9f9e5f3d461484acacf388c2f25e2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99347-0https://doaj.org/toc/2045-2322Abstract Adoptive T-cell transfer (ACT) offers a curative therapeutic option for subsets of melanoma and hematological cancer patients. To increase response rates and broaden the applicability of ACT, it is necessary to improve the post-infusion performance of the transferred T cells. The design of improved treatment strategies includes transfer of cells with a less differentiated phenotype. Such T cell subsets have high proliferative potential but require stimulatory signals in vivo to differentiate into tumor-reactive effector T cells. Thus, combination strategies are needed to support the therapeutic implementation of less differentiated T cells. Here we show that systemic delivery of tumor-associated antigens (TAAs) facilitates in vivo priming and expansion of previously non-activated T cells and enhance the cytotoxicity of activated T cells. To achieve this in vivo priming, we use flexible delivery vehicles of TAAs and a TLR7/8 agonist. Contrasting subcutaneous delivery systems, these vehicles accumulate TAAs in the spleen, thereby achieving close proximity to both cross-presenting dendritic cells and transferred T cells, resulting in robust T-cell expansion and anti-tumor reactivity. This TAA delivery platform offers a strategy to safely potentiate the post-infusion performance of T cells using low doses of antigen and TLR7/8 agonist, and thereby enhance the effect of ACT.Ditte E. JæhgerMie L. HübbeMartin K. KræmerGael ClergeaudAndré V. OlsenCamilla StavnsbjergMette N. WiinholtAndreas KjærJonas R. HenriksenAnders E. HansenThomas L. AndresenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ditte E. Jæhger Mie L. Hübbe Martin K. Kræmer Gael Clergeaud André V. Olsen Camilla Stavnsbjerg Mette N. Wiinholt Andreas Kjær Jonas R. Henriksen Anders E. Hansen Thomas L. Andresen Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens
description	Abstract Adoptive T-cell transfer (ACT) offers a curative therapeutic option for subsets of melanoma and hematological cancer patients. To increase response rates and broaden the applicability of ACT, it is necessary to improve the post-infusion performance of the transferred T cells. The design of improved treatment strategies includes transfer of cells with a less differentiated phenotype. Such T cell subsets have high proliferative potential but require stimulatory signals in vivo to differentiate into tumor-reactive effector T cells. Thus, combination strategies are needed to support the therapeutic implementation of less differentiated T cells. Here we show that systemic delivery of tumor-associated antigens (TAAs) facilitates in vivo priming and expansion of previously non-activated T cells and enhance the cytotoxicity of activated T cells. To achieve this in vivo priming, we use flexible delivery vehicles of TAAs and a TLR7/8 agonist. Contrasting subcutaneous delivery systems, these vehicles accumulate TAAs in the spleen, thereby achieving close proximity to both cross-presenting dendritic cells and transferred T cells, resulting in robust T-cell expansion and anti-tumor reactivity. This TAA delivery platform offers a strategy to safely potentiate the post-infusion performance of T cells using low doses of antigen and TLR7/8 agonist, and thereby enhance the effect of ACT.
format	article
author	Ditte E. Jæhger Mie L. Hübbe Martin K. Kræmer Gael Clergeaud André V. Olsen Camilla Stavnsbjerg Mette N. Wiinholt Andreas Kjær Jonas R. Henriksen Anders E. Hansen Thomas L. Andresen
author_facet	Ditte E. Jæhger Mie L. Hübbe Martin K. Kræmer Gael Clergeaud André V. Olsen Camilla Stavnsbjerg Mette N. Wiinholt Andreas Kjær Jonas R. Henriksen Anders E. Hansen Thomas L. Andresen
author_sort	Ditte E. Jæhger
title	Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens
title_short	Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens
title_full	Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens
title_fullStr	Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens
title_full_unstemmed	Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens
title_sort	enhancing adoptive cd8 t cell therapy by systemic delivery of tumor associated antigens
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a35c9f9e5f3d461484acacf388c2f25e
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Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens

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