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

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Harvard

Kirkin, AF, Dzhandzhugazyan, KN, Guldberg, P, Fang, JJ, Andersen, RS, Dahl, C, Mortensen, J, Lundby, T, Wagner, A, Law, I, Broholm, H, Madsen, L, Lundell-Ek, C, Gjerstorff, MF, Ditzel, HJ, Jensen, MR & Fischer, W 2018, 'Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells', Nature Communications, bind 9, nr. 1, s. 785. https://doi.org/10.1038/s41467-018-03217-9

APA

Kirkin, A. F., Dzhandzhugazyan, K. N., Guldberg, P., Fang, J. J., Andersen, R. S., Dahl, C., Mortensen, J., Lundby, T., Wagner, A., Law, I., Broholm, H., Madsen, L., Lundell-Ek, C., Gjerstorff, M. F., Ditzel, H. J., Jensen, M. R., & Fischer, W. (2018). Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nature Communications, 9(1), 785. https://doi.org/10.1038/s41467-018-03217-9

CBE

Kirkin AF, Dzhandzhugazyan KN, Guldberg P, Fang JJ, Andersen RS, Dahl C, Mortensen J, Lundby T, Wagner A, Law I, Broholm H, Madsen L, Lundell-Ek C, Gjerstorff MF, Ditzel HJ, Jensen MR, Fischer W. 2018. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nature Communications. 9(1):785. https://doi.org/10.1038/s41467-018-03217-9

MLA

Vancouver

Author

Kirkin, Alexei F ; Dzhandzhugazyan, Karine N ; Guldberg, Per ; Fang, Johnny Jon ; Andersen, Rikke S ; Dahl, Christina ; Mortensen, Jann ; Lundby, Tim ; Wagner, Aase ; Law, Ian ; Broholm, Helle ; Madsen, Line ; Lundell-Ek, Christer ; Gjerstorff, Morten F ; Ditzel, Henrik J ; Jensen, Martin R ; Fischer, Walter. / Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. I: Nature Communications. 2018 ; Bind 9, Nr. 1. s. 785.

Bibtex

@article{2101d6939bf94e51af3ef537382982cb,
title = "Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells",
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.",
keywords = "Adult, Antigen-Presenting Cells/immunology, Antigens, Neoplasm/genetics, Brain Neoplasms/genetics, DNA/genetics, DNA Methylation, Female, Glioblastoma/genetics, Humans, Immunotherapy, Adoptive, Male, Prospective Studies, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Helper-Inducer/immunology, Young Adult",
author = "Kirkin, {Alexei F} and Dzhandzhugazyan, {Karine N} and Per Guldberg and Fang, {Johnny Jon} and Andersen, {Rikke S} and Christina Dahl and Jann Mortensen and Tim Lundby and Aase Wagner and Ian Law and Helle Broholm and Line Madsen and Christer Lundell-Ek and Gjerstorff, {Morten F} and Ditzel, {Henrik J} and Jensen, {Martin R} and Walter Fischer",
year = "2018",
month = mar,
day = "6",
doi = "10.1038/s41467-018-03217-9",
language = "English",
volume = "9",
pages = "785",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells

AU - Kirkin, Alexei F

AU - Dzhandzhugazyan, Karine N

AU - Guldberg, Per

AU - Fang, Johnny Jon

AU - Andersen, Rikke S

AU - Dahl, Christina

AU - Mortensen, Jann

AU - Lundby, Tim

AU - Wagner, Aase

AU - Law, Ian

AU - Broholm, Helle

AU - Madsen, Line

AU - Lundell-Ek, Christer

AU - Gjerstorff, Morten F

AU - Ditzel, Henrik J

AU - Jensen, Martin R

AU - Fischer, Walter

PY - 2018/3/6

Y1 - 2018/3/6

N2 - 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.

AB - 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.

KW - Adult

KW - Antigen-Presenting Cells/immunology

KW - Antigens, Neoplasm/genetics

KW - Brain Neoplasms/genetics

KW - DNA/genetics

KW - DNA Methylation

KW - Female

KW - Glioblastoma/genetics

KW - Humans

KW - Immunotherapy, Adoptive

KW - Male

KW - Prospective Studies

KW - T-Lymphocytes, Cytotoxic/immunology

KW - T-Lymphocytes, Helper-Inducer/immunology

KW - Young Adult

U2 - 10.1038/s41467-018-03217-9

DO - 10.1038/s41467-018-03217-9

M3 - Journal article

C2 - 29511178

VL - 9

SP - 785

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 55350890