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أعرض في EDS

TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial.

التفاصيل البيبلوغرافية
العنوان: TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial.
المؤلفون: Everson RG; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Hugo W; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Parker Institute for Cancer Immunotherapy, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Sun L; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Antonios J; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Lee A; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Ding L; Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Bu M; Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Khattab S; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Chavez C; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Billingslea-Yoon E; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Salazar A; Oncovir, Inc., Winchester, VA, USA., Ellingson BM; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Cloughesy TF; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Department of Neurology/Neuro-Oncology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA., Liau LM; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA. lliau@mednet.ucla.edu.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA. lliau@mednet.ucla.edu., Prins RM; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA. RPrins@mednet.ucla.edu.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA. RPrins@mednet.ucla.edu.; Parker Institute for Cancer Immunotherapy, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA. RPrins@mednet.ucla.edu.; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA. RPrins@mednet.ucla.edu.
المصدر: Nature communications [Nat Commun] 2024 May 08; Vol. 15 (1), pp. 3882. Date of Electronic Publication: 2024 May 08.
نوع المنشور: Journal Article; Clinical Trial, Phase II; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Dendritic Cells*/immunology , Dendritic Cells*/drug effects , Glioma*/immunology , Glioma*/therapy , Interferons* , Cancer Vaccines*/immunology , Cancer Vaccines*/administration & dosage , Cancer Vaccines*/therapeutic use , CD8-Positive T-Lymphocytes*/immunology , CD8-Positive T-Lymphocytes*/drug effects , Poly I-C*/administration & dosage , Poly I-C*/pharmacology, Carboxymethylcellulose Sodium/*analogs & derivatives , Polylysine/*analogs & derivatives, Humans ; Female ; Male ; Middle Aged ; Adult ; Toll-Like Receptors/agonists ; Imidazoles/pharmacology ; Imidazoles/therapeutic use ; Aged ; Vaccination ; Monocytes/immunology ; Monocytes/drug effects ; Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Brain Neoplasms/drug therapy ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/drug effects ; Immunotherapy/methods ; Toll-Like Receptor Agonists
مستخلص: In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.
(© 2024. The Author(s).)
التعليقات: Update of: Res Sq. 2023 Sep 12:rs.3.rs-3287211. doi: 10.21203/rs.3.rs-3287211/v1. (PMID: 37790490)
Erratum in: Nat Commun. 2024 Jun 5;15(1):4800. doi: 10.1038/s41467-024-48995-7. (PMID: 38839763)
References: Front Immunol. 2019 Apr 09;10:725. (PMID: 31024557)
Nature. 2017 May 25;545(7655):452-456. (PMID: 28514453)
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517)
Nat Rev Cancer. 2021 Jun;21(6):345-359. (PMID: 33837297)
Nature. 2007 Oct 18;449(7164):819-26. (PMID: 17943118)
Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700)
J Immunother Cancer. 2020 Sep;8(2):. (PMID: 32958686)
Clin Cancer Res. 2018 Oct 15;24(20):4937-4948. (PMID: 29950349)
Oncologist. 2008 Aug;13(8):859-75. (PMID: 18701762)
Eur J Cancer. 2022 Oct;174:10-20. (PMID: 35970031)
J Immunol. 2003 Sep 15;171(6):3154-62. (PMID: 12960343)
J Immunol. 2013 Apr 15;190(8):4103-15. (PMID: 23509365)
J Transl Med. 2007 Feb 12;5:10. (PMID: 17295916)
Neuro Oncol. 2015 Sep;17(9):1188-98. (PMID: 26250565)
J Neurooncol. 2009 Jan;91(2):175-82. (PMID: 18797818)
Clin Cancer Res. 2011 Mar 15;17(6):1603-15. (PMID: 21135147)
Nat Immunol. 2023 Feb;24(2):267-279. (PMID: 36543958)
Glia. 2005 Feb;49(3):360-74. (PMID: 15538753)
JAMA Oncol. 2020 Jul 1;6(7):1003-1010. (PMID: 32437507)
Immunity. 2011 Feb 25;34(2):213-23. (PMID: 21349431)
Cytokine Growth Factor Rev. 2011 Apr;22(2):63-72. (PMID: 21466970)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Radiology. 2014 Apr;271(1):200-10. (PMID: 24475840)
Front Immunol. 2014 Sep 25;5:461. (PMID: 25309543)
J Immunol. 2003 Dec 1;171(11):6275-82. (PMID: 14634145)
Clin Cancer Res. 2005 Aug 1;11(15):5515-25. (PMID: 16061868)
Glia. 2006 May;53(7):688-95. (PMID: 16482523)
Immunity. 2019 Jan 15;50(1):195-211.e10. (PMID: 30635237)
Vaccine. 2010 Aug 31;28(38):6273-81. (PMID: 20637759)
Nat Med. 2018 Feb;24(2):144-153. (PMID: 29309059)
Neurosurgery. 1996 Jun;38(6):1096-103; discussion 1103-4. (PMID: 8727138)
F1000Res. 2017 May 26;6:748. (PMID: 28663787)
Lancet Oncol. 2009 May;10(5):459-66. (PMID: 19269895)
Blood. 2010 Mar 11;115(10):1949-57. (PMID: 20065291)
J Transl Med. 2018 May 29;16(1):142. (PMID: 29843811)
Invest New Drugs. 2001;19(1):89-92. (PMID: 11291838)
Cancer Immunol Immunother. 2010 Sep;59(9):1401-9. (PMID: 20549206)
Cancer Immunol Immunother. 2018 Jul;67(7):1091-1103. (PMID: 29696308)
Nat Biotechnol. 2018 Jun;36(5):411-420. (PMID: 29608179)
J Immunol. 2004 Sep 15;173(6):3916-24. (PMID: 15356140)
Nat Rev Clin Oncol. 2021 Nov;18(11):729-744. (PMID: 34117475)
Vaccine. 2009 Sep 25;27(42):5791-9. (PMID: 19660592)
JAMA Oncol. 2023 Jan 1;9(1):112-121. (PMID: 36394838)
J Clin Oncol. 2011 Jan 20;29(3):330-6. (PMID: 21149657)
Front Immunol. 2021 Feb 02;11:622509. (PMID: 33633741)
BMC Bioinformatics. 2013 Jan 16;14:7. (PMID: 23323831)
J Immunol. 2006 Jan 1;176(1):157-64. (PMID: 16365406)
Cancer. 2016 Jun 1;122(11):1718-27. (PMID: 26998740)
Neuro Oncol. 2018 Sep 3;20(10):1411-1418. (PMID: 29660005)
J Neuroimmunol. 2005 Feb;159(1-2):12-9. (PMID: 15652398)
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7. (PMID: 27141961)
Nat Methods. 2015 Apr;12(4):357-60. (PMID: 25751142)
J Clin Oncol. 2010 Apr 10;28(11):1963-72. (PMID: 20231676)
Cancer Res. 2018 Jan 1;78(1):115-128. (PMID: 29066514)
Nat Immunol. 2015 Dec;16(12):1215-27. (PMID: 26479788)
N Engl J Med. 2008 Jul 31;359(5):539-41. (PMID: 18669440)
Oncogene. 2008 Jan 7;27(2):218-24. (PMID: 18176603)
J Endotoxin Res. 2005;11(6):369-74. (PMID: 16303093)
J Neuroimmunol. 2005 Dec;169(1-2):116-25. (PMID: 16146656)
Oncogene. 2008 Jan 7;27(2):181-9. (PMID: 18176599)
معلومات مُعتمدة: R01 CA123396 United States CA NCI NIH HHS; P30 CA016042 United States CA NCI NIH HHS; T32 CA009120 United States CA NCI NIH HHS; P50 CA211015 United States CA NCI NIH HHS; UL1 TR001881 United States TR NCATS NIH HHS; R01 CA236910 United States CA NCI NIH HHS
سلسلة جزيئية: ClinicalTrials.gov NCT01204684
المشرفين على المادة: 7KYP9TKT70 (poly ICLC)
9008-11-1 (Interferons)
0 (Cancer Vaccines)
O84C90HH2L (Poly I-C)
V3DMU7PVXF (resiquimod)
0 (Toll-Like Receptors)
0 (Imidazoles)
0 (Toll-Like Receptor Agonists)
K679OBS311 (Carboxymethylcellulose Sodium)
25104-18-1 (Polylysine)
تواريخ الأحداث: Date Created: 20240508 Date Completed: 20240508 Latest Revision: 20240608
رمز التحديث: 20240608
مُعرف محوري في PubMed: PMC11078958
DOI: 10.1038/s41467-024-48073-y
PMID: 38719809
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-48073-y