Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model

Abstract DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specific cytotoxic T cells into tumours. Cancer cells upregulate phosphatidylserine (PS) on the cell surface as a mechanism to induce an immunosuppressive microenvironment. Development of anti-PS targe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Brennan S. Dirk, Genevieve Weir, Tara Quinton, Olga Hrytsenko, Marianne M. Stanford
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b62c45020a740c6ba50d1260acc9877
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5b62c45020a740c6ba50d1260acc9877
record_format	dspace
spelling	oai:doaj.org-article:5b62c45020a740c6ba50d1260acc98772021-12-02T13:20:21ZCombination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model10.1038/s41598-021-82108-42045-2322https://doaj.org/article/5b62c45020a740c6ba50d1260acc98772021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82108-4https://doaj.org/toc/2045-2322Abstract DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specific cytotoxic T cells into tumours. Cancer cells upregulate phosphatidylserine (PS) on the cell surface as a mechanism to induce an immunosuppressive microenvironment. Development of anti-PS targeting antibodies have highlighted the ability of a PS-blockade to enhance tumour control by T cells by releasing immunosuppression. Here, C57BL/6 mice were implanted with HPV16 E7 target-expressing C3 tumours and subjected to low dose intermittent cyclophosphamide (CPA) in combination with DPX-R9F treatment targeting an E7 antigen with and without anti-PS and/or anti-PD-1 targeting antibodies. Immune responses were assessed via IFN-γ ELISPOT assay and the tumour microenvironment was further analyzed using RT-qPCR. We show that the combination of DPX-R9F and PS-targeting antibodies with and without anti-PD-1 demonstrated increased efficacy compared to untreated controls. All treatments containing DPX-R9F led to T cell activation as assessed by IFN-γ ELISPOT. Furthermore, DPX-R9F/anti-PS treatment significantly elevated cytotoxic T cells, macrophages and dendritic cells based on RT-qPCR analysis. Overall, our data indicates that anti-tumour responses are driven through a variety of immune cells within this model and highlights the need to investigate combination therapies which increase tumour immune infiltration, such as anti-phosphotidylserine.Brennan S. DirkGenevieve WeirTara QuintonOlga HrytsenkoMarianne M. StanfordNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brennan S. Dirk Genevieve Weir Tara Quinton Olga Hrytsenko Marianne M. Stanford Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
description	Abstract DPX is a novel delivery platform that generates targeted CD8 + T cells and drives antigen-specific cytotoxic T cells into tumours. Cancer cells upregulate phosphatidylserine (PS) on the cell surface as a mechanism to induce an immunosuppressive microenvironment. Development of anti-PS targeting antibodies have highlighted the ability of a PS-blockade to enhance tumour control by T cells by releasing immunosuppression. Here, C57BL/6 mice were implanted with HPV16 E7 target-expressing C3 tumours and subjected to low dose intermittent cyclophosphamide (CPA) in combination with DPX-R9F treatment targeting an E7 antigen with and without anti-PS and/or anti-PD-1 targeting antibodies. Immune responses were assessed via IFN-γ ELISPOT assay and the tumour microenvironment was further analyzed using RT-qPCR. We show that the combination of DPX-R9F and PS-targeting antibodies with and without anti-PD-1 demonstrated increased efficacy compared to untreated controls. All treatments containing DPX-R9F led to T cell activation as assessed by IFN-γ ELISPOT. Furthermore, DPX-R9F/anti-PS treatment significantly elevated cytotoxic T cells, macrophages and dendritic cells based on RT-qPCR analysis. Overall, our data indicates that anti-tumour responses are driven through a variety of immune cells within this model and highlights the need to investigate combination therapies which increase tumour immune infiltration, such as anti-phosphotidylserine.
format	article
author	Brennan S. Dirk Genevieve Weir Tara Quinton Olga Hrytsenko Marianne M. Stanford
author_facet	Brennan S. Dirk Genevieve Weir Tara Quinton Olga Hrytsenko Marianne M. Stanford
author_sort	Brennan S. Dirk
title	Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
title_short	Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
title_full	Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
title_fullStr	Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
title_full_unstemmed	Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model
title_sort	combination of a t cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a hpv16 e7-expressing c3 tumour model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b62c45020a740c6ba50d1260acc9877
work_keys_str_mv	AT brennansdirk combinationofatcellactivatingtherapyandantiphosphatidylserineenhancesantitumourimmuneresponsesinahpv16e7expressingc3tumourmodel AT genevieveweir combinationofatcellactivatingtherapyandantiphosphatidylserineenhancesantitumourimmuneresponsesinahpv16e7expressingc3tumourmodel AT taraquinton combinationofatcellactivatingtherapyandantiphosphatidylserineenhancesantitumourimmuneresponsesinahpv16e7expressingc3tumourmodel AT olgahrytsenko combinationofatcellactivatingtherapyandantiphosphatidylserineenhancesantitumourimmuneresponsesinahpv16e7expressingc3tumourmodel AT mariannemstanford combinationofatcellactivatingtherapyandantiphosphatidylserineenhancesantitumourimmuneresponsesinahpv16e7expressingc3tumourmodel
_version_	1718393213189881856

Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model

Ejemplares similares