Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells.

Autor:	Kirkin AF; Danish Cancer Society Research Center, 2100, Copenhagen, Denmark. aki@cytovac.dk.; CytoVac A/S, 2970, Hørsholm, Denmark. aki@cytovac.dk., Dzhandzhugazyan KN; Danish Cancer Society Research Center, 2100, Copenhagen, Denmark.; CytoVac A/S, 2970, Hørsholm, Denmark., Guldberg P; Danish Cancer Society Research Center, 2100, Copenhagen, Denmark., Fang JJ; Danish Cancer Society Research Center, 2100, Copenhagen, Denmark.; CytoVac A/S, 2970, Hørsholm, Denmark., Andersen RS; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000, Odense, Denmark., Dahl C; Danish Cancer Society Research Center, 2100, Copenhagen, Denmark., Mortensen J; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark., Lundby T; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark., Wagner A; Department of Neuroradiology, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark., Law I; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark., Broholm H; Department of Neuropathology, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark., Madsen L; Department of Pathology, Aarhus University Hospital, 8000, Aarhus, Denmark., Lundell-Ek C; CytoVac A/S, 2970, Hørsholm, Denmark., Gjerstorff MF; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000, Odense, Denmark., Ditzel HJ; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000, Odense, Denmark.; Department of Oncology, Odense University Hospital, 5000, Odense, Denmark., Jensen MR; CytoVac A/S, 2970, Hørsholm, Denmark., Fischer W; CytoVac A/S, 2970, Hørsholm, Denmark.; Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Mar 06; Vol. 9 (1), pp. 785. Date of Electronic Publication: 2018 Mar 06.
DOI:	10.1038/s41467-018-03217-9
Abstrakt:	In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4 + T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25 patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can be generated ex vivo by exposure to antigens induced by DNA demethylation, providing a novel, minimally invasive therapeutic strategy for treating cancer.
Databáze:	MEDLINE
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