Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Alexei F. Kirkin, Karine N. Dzhandzhugazyan, Per Guldberg, Johnny Jon Fang, Rikke S. Andersen, Christina Dahl, Jann Mortensen, Tim Lundby, Aase Wagner, Ian Law, Helle Broholm, Line Madsen, Christer Lundell-Ek, Morten F. Gjerstorff, Henrik J. Ditzel, Martin R. Jensen, Walter Fischer

ABSTRACT

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. More... »

PAGES

785

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-03217-9

DOI

http://dx.doi.org/10.1038/s41467-018-03217-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101113689

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29511178


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