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

Research output: Contribution to journal › Journal article › Research › peer-review

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

In: Nature Communications, Vol. 9, 785, 2018.

Research output: Contribution to journal › Journal article › Research › peer-review

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, vol. 9, 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, [785]. https://doi.org/10.1038/s41467-018-03217-9

Vancouver

Kirkin AF, Dzhandzhugazyan KN, Guldberg P, Fang JJ, Andersen RS, Dahl C et al. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nature Communications. 2018;9. 785. https://doi.org/10.1038/s41467-018-03217-9

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. In: Nature Communications. 2018 ; Vol. 9.

Bibtex

@article{4c776294530f46c18faf77b1740a7a6b,
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",
doi = "10.1038/s41467-018-03217-9",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

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

Y1 - 2018

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

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 785

ER -

ID: 216470758