دورية أكاديمية
أعرض في EDS

Mathematical modeling of N-803 treatment in SIV-infected non-human primates.

التفاصيل البيبلوغرافية
العنوان: Mathematical modeling of N-803 treatment in SIV-infected non-human primates.
المؤلفون: Cody JW; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America., Ellis-Connell AL; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., O'Connor SL; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Pienaar E; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
المصدر: PLoS computational biology [PLoS Comput Biol] 2021 Jul 28; Vol. 17 (7), pp. e1009204. Date of Electronic Publication: 2021 Jul 28 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2005]-
مواضيع طبية MeSH: Models, Biological*, Interleukin-15/*agonists , Recombinant Fusion Proteins/*therapeutic use , Simian Acquired Immunodeficiency Syndrome/*therapy, Animals ; CD8-Positive T-Lymphocytes/immunology ; Computational Biology ; Humans ; Immune Tolerance ; Killer Cells, Natural/immunology ; Macaca mulatta ; Mathematical Concepts ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/immunology ; Simian Immunodeficiency Virus/pathogenicity ; Simian Immunodeficiency Virus/physiology ; Viral Load ; Virus Replication
مستخلص: Immunomodulatory drugs could contribute to a functional cure for Human Immunodeficiency Virus (HIV). Interleukin-15 (IL-15) promotes expansion and activation of CD8+ T cell and natural killer (NK) cell populations. In one study, an IL-15 superagonist, N-803, suppressed Simian Immunodeficiency Virus (SIV) in non-human primates (NHPs) who had received prior SIV vaccination. However, viral suppression attenuated with continued N-803 treatment, partially returning after long treatment interruption. While there is evidence of concurrent drug tolerance, immune regulation, and viral escape, the relative contributions of these mechanisms to the observed viral dynamics have not been quantified. Here, we utilize mathematical models of N-803 treatment in SIV-infected macaques to estimate contributions of these three key mechanisms to treatment outcomes: 1) drug tolerance, 2) immune regulation, and 3) viral escape. We calibrated our model to viral and lymphocyte responses from the above-mentioned NHP study. Our models track CD8+ T cell and NK cell populations with N-803-dependent proliferation and activation, as well as viral dynamics in response to these immune cell populations. We compared mathematical models with different combinations of the three key mechanisms based on Akaike Information Criterion and important qualitative features of the NHP data. Two minimal models were capable of reproducing the observed SIV response to N-803. In both models, immune regulation strongly reduced cytotoxic cell activation to enable viral rebound. Either long-term drug tolerance or viral escape (or some combination thereof) could account for changes to viral dynamics across long breaks in N-803 treatment. Theoretical explorations with the models showed that less-frequent N-803 dosing and concurrent immune regulation blockade (e.g. PD-L1 inhibition) may improve N-803 efficacy. However, N-803 may need to be combined with other immune therapies to countermand viral escape from the CD8+ T cell response. Our mechanistic model will inform such therapy design and guide future studies.
Competing Interests: The authors have declared that no competing interests exist.
References: PLoS Comput Biol. 2008 Jul 18;4(7):e1000103. (PMID: 18636096)
J Virol. 2011 Dec;85(24):13088-96. (PMID: 21994463)
Oncotarget. 2016 Mar 29;7(13):16130-45. (PMID: 26910920)
Retrovirology. 2018 Jan 30;15(1):14. (PMID: 29378595)
J Virol. 2015 Nov;89(21):10802-20. (PMID: 26292326)
Immunol Rev. 2018 Sep;285(1):9-25. (PMID: 30129208)
J Immunol. 2006 Nov 1;177(9):6072-80. (PMID: 17056533)
Immunol Lett. 2015 Nov;168(1):1-6. (PMID: 26279491)
Lancet Oncol. 2018 May;19(5):694-704. (PMID: 29628312)
Oncotarget. 2017 Jul 4;8(27):44366-44378. (PMID: 28574833)
Curr HIV Res. 2016;14(2):110-20. (PMID: 26511341)
J Virol. 2014 Dec;88(24):14050-6. (PMID: 25253352)
PLoS Pathog. 2018 Feb 23;14(2):e1006902. (PMID: 29474450)
J Infect Dis. 2017 Jun 1;215(11):1725-1733. (PMID: 28431010)
J Virol. 2004 Sep;78(18):10096-103. (PMID: 15331742)
J Virol. 2013 Aug;87(16):9353-64. (PMID: 23785211)
Adv Exp Med Biol. 2018;1075:165-185. (PMID: 30030793)
BMC Biol. 2013 Sep 03;11:96. (PMID: 24020860)
Cancer Immunol Res. 2016 Jan;4(1):49-60. (PMID: 26511282)
Immunity. 2018 Apr 17;48(4):760-772.e4. (PMID: 29625893)
Nature. 2020 Feb;578(7793):154-159. (PMID: 31969705)
Nat Commun. 2019 Feb 18;10(1):814. (PMID: 30778080)
Nature. 2016 Dec 8;540(7632):284-287. (PMID: 27841870)
J Virol. 2018 Jan 17;92(3):. (PMID: 29118125)
Viral Immunol. 2017 Jan/Feb;30(1):3-12. (PMID: 27805477)
Annu Rev Immunol. 2000;18:83-111. (PMID: 10837053)
Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19727-32. (PMID: 23112156)
PLoS Comput Biol. 2019 Nov 6;15(11):e1007401. (PMID: 31693657)
PLoS Pathog. 2016 Apr 15;12(4):e1005545. (PMID: 27082643)
AIDS Res Ther. 2017 Sep 12;14(1):45. (PMID: 28893280)
Front Immunol. 2018 Jan 25;9:20. (PMID: 29422894)
J Immunol. 2010 Sep 15;185(6):3436-44. (PMID: 20733203)
PLoS Comput Biol. 2016 Jan 06;12(1):e1004677. (PMID: 26735135)
Cancer Biother Radiopharm. 2019 Apr;34(3):147-159. (PMID: 30601063)
Oncoimmunology. 2018 Nov 27;8(2):e1532764. (PMID: 30713787)
J Virol. 2005 Apr;79(8):4877-85. (PMID: 15795273)
PLoS One. 2012;7(4):e33924. (PMID: 22536321)
Sci Transl Med. 2019 Dec 18;11(523):. (PMID: 31852798)
J Exp Med. 1999 Mar 15;189(6):991-8. (PMID: 10075982)
Folia Microbiol (Praha). 2017 Jan;62(1):73-87. (PMID: 27709447)
Nature. 2009 Mar 12;458(7235):206-10. (PMID: 19078956)
Science. 2016 May 20;352(6288):1001-4. (PMID: 27199430)
PLoS Biol. 2006 Apr;4(4):e90. (PMID: 16515366)
PLoS Pathog. 2017 Jul 5;13(7):e1006478. (PMID: 28678879)
J Clin Invest. 2012 May;122(5):1712-6. (PMID: 22523065)
Immunol Lett. 2017 Oct;190:159-168. (PMID: 28823521)
Nature. 1991 Dec 12;354(6353):453-9. (PMID: 1721107)
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6365-70. (PMID: 17404226)
J Theor Biol. 2011 Nov 21;289:17-35. (PMID: 21871901)
Cytokine. 2011 Dec;56(3):804-10. (PMID: 22019703)
Front Immunol. 2019 Jul 24;10:1749. (PMID: 31396237)
J Virol. 2007 Aug;81(16):8827-32. (PMID: 17537848)
Curr Top Microbiol Immunol. 2016;392:277-302. (PMID: 26174625)
Curr HIV Res. 2006 Apr;4(2):191-7. (PMID: 16611057)
Trends Mol Med. 2017 Oct;23(10):945-961. (PMID: 28890135)
Cytokine Growth Factor Rev. 2016 Oct;31:49-59. (PMID: 27325459)
J Immunol. 2009 Sep 15;183(6):3598-607. (PMID: 19710453)
Blood. 2018 Jun 7;131(23):2515-2527. (PMID: 29463563)
J Immunol. 2008 Jan 1;180(1):350-60. (PMID: 18097036)
Nat Med. 2004 Mar;10(3):275-81. (PMID: 14966520)
J Biol Dyn. 2008 Oct;2(4):357-85. (PMID: 19495424)
BMC Infect Dis. 2017 Aug 29;17(1):595. (PMID: 28851294)
Nat Rev Immunol. 2004 Aug;4(8):630-40. (PMID: 15286729)
Front Immunol. 2018 Nov 09;9:2569. (PMID: 30473697)
Science. 2006 Apr 7;312(5770):114-6. (PMID: 16513943)
Nature. 2000 Sep 21;407(6802):386-90. (PMID: 11014195)
Nature. 2018 Nov;563(7731):360-364. (PMID: 30283138)
J Immunol. 2011 Apr 15;186(8):4590-8. (PMID: 21402893)
J Immunol. 2003 Mar 1;170(5):2479-87. (PMID: 12594273)
Clin Cancer Res. 2016 Feb 1;22(3):596-608. (PMID: 26423796)
J Virol. 2006 May;80(10):5074-7. (PMID: 16641299)
Bioinformatics. 2018 Feb 15;34(4):705-707. (PMID: 29069312)
Clin Cancer Res. 2018 Nov 15;24(22):5552-5561. (PMID: 30045932)
J Leukoc Biol. 2019 Jun;105(6):1253-1259. (PMID: 30730588)
Oncotarget. 2016 Jan 5;7(1):814-30. (PMID: 26625316)
J Virol. 2008 Jul;82(13):6758-61. (PMID: 18434394)
PLoS Pathog. 2020 Mar 12;16(3):e1008339. (PMID: 32163523)
Cancer Immunol Immunother. 2018 Apr;67(4):675-689. (PMID: 29392336)
Blood Adv. 2018 Jan 23;2(2):76-84. (PMID: 29365313)
J Exp Med. 2001 Oct 1;194(7):953-66. (PMID: 11581317)
J Theor Biol. 2015 May 7;372:146-58. (PMID: 25701451)
معلومات مُعتمدة: R01 AI108415 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (ALT-803)
0 (IL15 protein, human)
0 (Interleukin-15)
0 (Recombinant Fusion Proteins)
تواريخ الأحداث: Date Created: 20210728 Date Completed: 20211025 Latest Revision: 20211025
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8351941
DOI: 10.1371/journal.pcbi.1009204
PMID: 34319980
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7358
DOI:10.1371/journal.pcbi.1009204