Show simple item record

dc.contributor.authorOwens, Gemma L
dc.contributor.authorPrice, M
dc.contributor.authorCheadle, Eleanor J
dc.contributor.authorHawkins, Rob
dc.contributor.authorGilham, David E
dc.contributor.authorEdmondson, R
dc.date.accessioned2018-08-19T14:12:10Z
dc.date.available2018-08-19T14:12:10Z
dc.date.issued2018-07-23
dc.identifier.citationEx vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells. 2018, Cancer Immunol Immunotheren
dc.identifier.issn1432-0851
dc.identifier.pmid30039427
dc.identifier.doi10.1007/s00262-018-2211-3
dc.identifier.urihttp://hdl.handle.net/10541/621174
dc.description.abstractEpithelial ovarian cancer (EOC) is the leading cause of gynaecological cancer-related death in Europe. Although most patients achieve an initial complete response with first-line treatment, recurrence occurs in more than 80% of cases. Thus, there is a clear unmet need for novel second-line treatments. EOC is frequently infiltrated with T lymphocytes, the presence of which has been shown to be associated with improved clinical outcomes. Adoptive T-cell therapy (ACT) using ex vivo-expanded tumour-infiltrating lymphocytes (TILs) has shown remarkable efficacy in other immunogenic tumours, and may represent a promising therapeutic strategy for EOC. In this preclinical study, we investigated the efficacy of using anti-CD3/anti-CD28 magnetic beads and IL-2 to expand TILs from freshly resected ovarian tumours. TILs were expanded for up to 3 weeks, and then subjected to a rapid-expansion protocol (REP) using irradiated feeder cells. Tumours were collected from 45 patients with EOC and TILs were successfully expanded from 89.7% of biopsies. Expanded CD4+ and CD8+ subsets demonstrated features associated with memory phenotypes, and had significantly higher expression of key activation and functional markers than unexpanded TILs. Expanded TILs produced anti-tumour cytokines when co-cultured with autologous tumour cells, inferring tumour cytotoxicity. Our findings demonstrate that it is possible to re-activate and expand tumour-reactive T cells from ovarian tumours. This presents a promising immunotherapy that could be used sequentially or in combination with current therapeutic strategies.
dc.language.isoenen
dc.rightsArchived with thanks to Cancer immunology, immunotherapy : CIIen
dc.titleEx vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells.en
dc.typeArticleen
dc.contributor.departmentGynaecological Oncology, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UKen
dc.identifier.journalCancer Immunology, Immunotherapyen
refterms.dateFOA2018-12-17T15:29:59Z
html.description.abstractEpithelial ovarian cancer (EOC) is the leading cause of gynaecological cancer-related death in Europe. Although most patients achieve an initial complete response with first-line treatment, recurrence occurs in more than 80% of cases. Thus, there is a clear unmet need for novel second-line treatments. EOC is frequently infiltrated with T lymphocytes, the presence of which has been shown to be associated with improved clinical outcomes. Adoptive T-cell therapy (ACT) using ex vivo-expanded tumour-infiltrating lymphocytes (TILs) has shown remarkable efficacy in other immunogenic tumours, and may represent a promising therapeutic strategy for EOC. In this preclinical study, we investigated the efficacy of using anti-CD3/anti-CD28 magnetic beads and IL-2 to expand TILs from freshly resected ovarian tumours. TILs were expanded for up to 3 weeks, and then subjected to a rapid-expansion protocol (REP) using irradiated feeder cells. Tumours were collected from 45 patients with EOC and TILs were successfully expanded from 89.7% of biopsies. Expanded CD4+ and CD8+ subsets demonstrated features associated with memory phenotypes, and had significantly higher expression of key activation and functional markers than unexpanded TILs. Expanded TILs produced anti-tumour cytokines when co-cultured with autologous tumour cells, inferring tumour cytotoxicity. Our findings demonstrate that it is possible to re-activate and expand tumour-reactive T cells from ovarian tumours. This presents a promising immunotherapy that could be used sequentially or in combination with current therapeutic strategies.


Files in this item

Thumbnail
Name:
Owens2018_Article_ExVivoExpand ...
Size:
2.248Mb
Format:
PDF
Description:
Full text, Open Access article

This item appears in the following Collection(s)

Show simple item record