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Title: Targeted epigenetic induction of mitochondrial biogenesis enhances antitumor immunity in mouse model
Authors: Malinee, Madhu
Namasivayam, Ganesh Pandian
Sugiyama, Hiroshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: ナマシヴァヤム, ガネシュ・パンディアン
杉山, 弘
Keywords: pyrrole-imidazole polyamide
epigenetic activator
cancer immunotherapy
mitochondrial biogenesis
oxidative phosphorylation
T-cell activation
combination therapy
therapeutic gene modulation
Issue Date: Mar-2022
Publisher: Elsevier BV
Journal title: Cell Chemical Biology
Volume: 29
Issue: 3
Start page: 463
End page: 475
Thesis number: e6
Abstract: Considering the potential of combinatorial therapies in overcoming existing limitations of cancer immunotherapy, there is an increasing need to identify small-molecule modulators of immune cells capable of augmenting the effect of programmed cell death protein 1 (PD-1) blockade, leading to better cancer treatment. Although epigenetic drugs showed potential in combination therapy, the lack of sequence specificity is a major concern. Here, we identify and develop a DNA-based epigenetic activator with tri-arginine vector called EnPGC-1 that can trigger the targeted induction of the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha/beta (PGC-1α/β), a regulator of mitochondrial biogenesis. EnPGC-1 enhances mitochondrial activation, energy metabolism, proliferation of CD8⁺ T cells in vitro, and, in particular, enhances oxidative phosphorylation, a feature of long-lived memory T cells. Genome-wide gene analysis suggests that EnPGC-1 and not the control compounds can regulate T cell activation as a major biological process. EnPGC-1 also synergizes with PD-1 blockade to enhance antitumor immunity and improved host survival.
Description: PD-1阻害剤によるがん免疫治療法の効果を高めるミトコンドリア活性化剤. 京都大学プレスリリース. 2021-09-14.
Cancer immunotherapy gets PIP boost. 京都大学プレスリリース. 2021-09-14.
Rights: © 2021. This manuscript version is made available under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International 4.0 license.
The full-text file will be made open to the public on 17 March 2023 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1016/j.chembiol.2021.08.001
PubMed ID: 34520746
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