%0 Journal Article %1 Kirkin:2018:Nat-Commun:29511178 %A Kirkin, A F %A Dzhandzhugazyan, K N %A Guldberg, P %A Fang, J J %A Andersen, R S %A Dahl, C %A Mortensen, J %A Lundby, T %A Wagner, A %A Law, I %A Broholm, H %A Madsen, L %A Lundell-Ek, C %A Gjerstorff, M F %A Ditzel, H J %A Jensen, M R %A Fischer, W %D 2018 %J Nat Commun %K SHOULDREAD astrocytoma cancer-research fulltext glioblastoma immunotherapy therapy %N 1 %P 785-785 %R 10.1038/s41467-018-03217-9 %T Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells %U https://www.ncbi.nlm.nih.gov/pubmed/29511178 %V 9 %X 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.

@article{Kirkin:2018:Nat-Commun:29511178, 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.}, added-at = {2018-05-18T19:32:28.000+0200}, author = {Kirkin, A F and Dzhandzhugazyan, K N and Guldberg, P and Fang, J J and Andersen, R S and Dahl, C and Mortensen, J and Lundby, T and Wagner, A and Law, I and Broholm, H and Madsen, L and Lundell-Ek, C and Gjerstorff, M F and Ditzel, H J and Jensen, M R and Fischer, W}, biburl = {https://www.bibsonomy.org/bibtex/2b74cf0c7d5016c469b320a329e0a298e/marcsaric}, description = {Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. - PubMed - NCBI}, doi = {10.1038/s41467-018-03217-9}, interhash = {ca44536bb0bfad1d51168dd432449435}, intrahash = {b74cf0c7d5016c469b320a329e0a298e}, journal = {Nat Commun}, keywords = {SHOULDREAD astrocytoma cancer-research fulltext glioblastoma immunotherapy therapy}, month = {03}, number = 1, pages = {785-785}, pmid = {29511178}, timestamp = {2018-05-18T19:32:28.000+0200}, title = {Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29511178}, volume = 9, year = 2018 }