Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function.

Autor: Ollé Hurtado M; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Wolbert J; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Fisher J; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Flutter B; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Stafford S; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Barton J; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Jain N; Department of Oncology, Great Ormond Street Hospital, London, England, United Kingdom., Barone G; Department of Oncology, Great Ormond Street Hospital, London, England, United Kingdom., Majani Y; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom., Anderson J; Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, England, United Kingdom.; Department of Oncology, Great Ormond Street Hospital, London, England, United Kingdom.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Aug 09; Vol. 14 (8), pp. e0216373. Date of Electronic Publication: 2019 Aug 09 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0216373
Abstrakt: Adoptive transfer of ex vivo expanded tumor infiltrating lymphocytes (TILs) has led to clinical benefit in some patients with melanoma but has not demonstrated convincing efficacy in other solid cancers. Whilst the presence of TILs in many types of cancer is often associated with better clinical prognosis, their function has not been systematically evaluated across cancer types. Responses to immunological checkpoint inhibitors in a wide range of cancers, including those for which adoptive transfer of expanded TILs has not shown clinical benefit, has clearly delineated a number of tumor type associated with tumor-reactive lymphocytes capable of effecting tumor remissions. Neuroblastoma is an aggressive childhood solid cancer in which immunotherapy with GD2-directed antibodies confers a proven survival advantage through incompletely understood mechanisms. We therefore evaluated the feasibility of ex vivo expansion of TILs from freshly resected neuroblastoma tumors and the potential therapeutic utility of TIL expansions. TILs were successfully expanded from both tumor biopsies or resections. Significant numbers of NKT and γδT cells were identified alongside the mixed population of cytotoxic (CD8+) and helper (CD4+) T cells of both effector and central memory phenotypes. Isolated TILs were broadly non-reactive against autologous tumor and neuroblastoma cell lines, so enhancement of neuroblastoma killing was attained by transducing TILs with a second-generation chimeric antigen receptor (CAR) targeting GD2. CAR-TILs demonstrated antigen-specific cytotoxicity against tumor cell lines. This study is the first to show reproducible expansion of TILs from pediatric neuroblastoma, the high proportion of innate-like lymphocytes, and the feasibility to use CAR-TILs therapeutically.
Competing Interests: John Anderson holds company stock in Autolus Ltd and is a paid consultant for TC Biopharm. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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