Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity

Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxy...

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Veröffentlicht in:Oncology letters 2018-04, Vol.15 (4), p.5105-5110
Hauptverfasser: Gao, Dong, Cai, Yongguang, Chen, Yanyuan, Li, Wang, Wei, Chih-Chang, Luo, Xiaoling, Wang, Yuhuan
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container_end_page 5110
container_issue 4
container_start_page 5105
container_title Oncology letters
container_volume 15
creator Gao, Dong
Cai, Yongguang
Chen, Yanyuan
Li, Wang
Wei, Chih-Chang
Luo, Xiaoling
Wang, Yuhuan
description Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells. The proportion of GD-induced CD3 CD56 CIK and CD3 CD56 NK cells was ~4% higher respectively compared with the control. Notably, combination therapy with CIK/NK cells stimulated by GD, markedly suppressed the proliferation of the chronic myelogenous leukemia K562 cell line. Following GD treatment, the cytotoxicity improved by ~25 and 21% when the effector/target ratio was 20:1 and 10:1, respectively. The results of the present study suggested a novel protocol for CIK/NK cell proliferation and revealed that GD may serve as a potent innate and adaptive immunomodulator in immunocyte culture.
doi_str_mv 10.3892/ol.2018.7954
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In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells. The proportion of GD-induced CD3 CD56 CIK and CD3 CD56 NK cells was ~4% higher respectively compared with the control. Notably, combination therapy with CIK/NK cells stimulated by GD, markedly suppressed the proliferation of the chronic myelogenous leukemia K562 cell line. Following GD treatment, the cytotoxicity improved by ~25 and 21% when the effector/target ratio was 20:1 and 10:1, respectively. The results of the present study suggested a novel protocol for CIK/NK cell proliferation and revealed that GD may serve as a potent innate and adaptive immunomodulator in immunocyte culture.</description><identifier>ISSN: 1792-1074</identifier><identifier>EISSN: 1792-1082</identifier><identifier>DOI: 10.3892/ol.2018.7954</identifier><identifier>PMID: 29552145</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Antigens ; Cancer ; Care and treatment ; Cell culture ; Chemotherapy ; Cytokines ; Cytotoxicity ; Health aspects ; Immunology ; Immunotherapy ; Ligands ; Lymphocytes ; Lymphoma ; Methods ; Oncology, Experimental ; Patient outcomes ; Pharmaceutical industry ; T cell receptors ; Toll-like receptors</subject><ispartof>Oncology letters, 2018-04, Vol.15 (4), p.5105-5110</ispartof><rights>COPYRIGHT 2018 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><rights>Copyright © 2018, Spandidos Publications 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c467t-c3615b9b4e08c5f1d22dbd1dd87a2e9c6f3b60714f850d5c900f1e7e34b25c013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840738/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840738/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29552145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Dong</creatorcontrib><creatorcontrib>Cai, Yongguang</creatorcontrib><creatorcontrib>Chen, Yanyuan</creatorcontrib><creatorcontrib>Li, Wang</creatorcontrib><creatorcontrib>Wei, Chih-Chang</creatorcontrib><creatorcontrib>Luo, Xiaoling</creatorcontrib><creatorcontrib>Wang, Yuhuan</creatorcontrib><title>Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity</title><title>Oncology letters</title><addtitle>Oncol Lett</addtitle><description>Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. 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source Spandidos Publications Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Antigens
Cancer
Care and treatment
Cell culture
Chemotherapy
Cytokines
Cytotoxicity
Health aspects
Immunology
Immunotherapy
Ligands
Lymphocytes
Lymphoma
Methods
Oncology, Experimental
Patient outcomes
Pharmaceutical industry
T cell receptors
Toll-like receptors
title Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity
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