Your browser doesn't support javascript.
loading
Ex vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells.
Owens, Gemma L; Price, Marcus J; Cheadle, Eleanor J; Hawkins, Robert E; Gilham, David E; Edmondson, Richard J.
Afiliação
  • Owens GL; Gynaecological Oncology, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
  • Price MJ; St Mary's Hospital, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Level 5, Research Floor, Oxford Road, Manchester, M13 9WL, UK.
  • Cheadle EJ; Clinical and Experimental Immunotherapy, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester Cancer Research Centre, University of Manchester, Wilmslow Road, Manchester, UK.
  • Hawkins RE; Gynaecological Oncology, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
  • Gilham DE; St Mary's Hospital, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Level 5, Research Floor, Oxford Road, Manchester, M13 9WL, UK.
  • Edmondson RJ; Targeted Therapy Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester Cancer Research Centre, University of Manchester, Wilmslow Road, Manchester, UK.
Cancer Immunol Immunother ; 67(10): 1519-1531, 2018 Oct.
Article em En | MEDLINE | ID: mdl-30039427
Epithelial 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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Carcinossarcoma / Citocinas / Imunoterapia Adotiva / Linfócitos do Interstício Tumoral / Cistadenocarcinoma Seroso / Adenocarcinoma de Células Claras Tipo de estudo: Guideline Limite: Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Carcinossarcoma / Citocinas / Imunoterapia Adotiva / Linfócitos do Interstício Tumoral / Cistadenocarcinoma Seroso / Adenocarcinoma de Células Claras Tipo de estudo: Guideline Limite: Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article