Biomimetic nanovaccine-mediated multivalent IL-15 self-transpresentation (MIST) for potent and safe cancer immunotherapy.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 10 2023
24 10 2023
Historique:
received:
08
01
2023
accepted:
02
10
2023
medline:
26
10
2023
pubmed:
25
10
2023
entrez:
24
10
2023
Statut:
epublish
Résumé
Cytokine therapy, involving interleukin-15 (IL-15), is a promising strategy for cancer immunotherapy. However, clinical application has been limited due to severe toxicity and the relatively low immune response rate, caused by wide distribution of cytokine receptors, systemic immune activation and short half-life of IL-15. Here we show that a biomimetic nanovaccine, developed to co-deliver IL-15 and an antigen/major histocompatibility complex (MHC) selectively targets IL-15 to antigen-specific cytotoxic T lymphocytes (CTL), thereby reducing off-target toxicity. The biomimetic nanovaccine is composed of cytomembrane vesicles, derived from genetically engineered dendritic cells (DC), onto which IL-15/IL-15 receptor α (IL-15Rα), tumor-associated antigenic (TAA) peptide/MHC-I, and relevant costimulatory molecules are simultaneously anchored. We demonstrate that, in contrast to conventional IL-15 therapy, the biomimetic nanovaccine with multivalent IL-15 self-transpresentation (biNV-IL-15) prolonged blood circulation of the cytokine with an 8.2-fold longer half-life than free IL-15 and improved the therapeutic window. This dual targeting strategy allows for spatiotemporal manipulation of therapeutic T cells, elicits broad spectrum antigen-specific T cell responses, and promotes cures in multiple syngeneic tumor models with minimal systemic side effects.
Identifiants
pubmed: 37875481
doi: 10.1038/s41467-023-42155-z
pii: 10.1038/s41467-023-42155-z
pmc: PMC10598200
doi:
Substances chimiques
Interleukin-15
0
Cytokines
0
Receptors, Interleukin-15
0
Cancer Vaccines
0
Banques de données
figshare
['10.6084/m9.figshare.24079164']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6748Informations de copyright
© 2023. Springer Nature Limited.
Références
Eur J Immunol. 2006 Jul;36(7):1772-81
pubmed: 16761310
Nat Commun. 2023 Oct 24;14(1):6748
pubmed: 37875481
Nat Rev Immunol. 2013 Apr;13(4):227-42
pubmed: 23470321
Trends Mol Med. 2014 Jan;20(1):16-24
pubmed: 24169116
Blood. 2003 Oct 1;102(7):2541-6
pubmed: 12805064
Curr Opin Chem Biol. 2006 Dec;10(6):537-43
pubmed: 17005436
Cell Res. 2021 Nov;31(11):1190-1198
pubmed: 34376814
J Exp Med. 2005 Jan 3;201(1):139-48
pubmed: 15630141
J Immunol. 2014 Jun 15;192(12):5451-8
pubmed: 24907378
Nat Nanotechnol. 2019 Jan;14(1):89-97
pubmed: 30531990
Nat Commun. 2023 May 23;14(1):2950
pubmed: 37221157
J Immunol Methods. 2022 Jun;505:113253
pubmed: 35358495
Blood. 2011 May 5;117(18):4787-95
pubmed: 21385847
Adv Sci (Weinh). 2019 Nov 08;7(1):1900069
pubmed: 31921548
ACS Nano. 2019 May 28;13(5):5662-5673
pubmed: 31046234
J Biol Chem. 2008 Feb 15;283(7):4189-99
pubmed: 18055460
CA Cancer J Clin. 2022 Jan;72(1):7-33
pubmed: 35020204
Nature. 2016 Jan 21;529(7586):298-306
pubmed: 26791720
Biomaterials. 2020 Oct;257:120224
pubmed: 32736255
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11671-6
pubmed: 16855047
Nat Rev Clin Oncol. 2022 Apr;19(4):237-253
pubmed: 34997230
Nat Commun. 2017 Nov 23;8(1):1747
pubmed: 29170511
Nat Immunol. 2012 Dec;13(12):1187-95
pubmed: 23104097
FEBS J. 2016 Jul;283(14):2731-48
pubmed: 26787424
Cancer Immunol Res. 2014 May;2(5):436-47
pubmed: 24795356
Semin Immunol. 2021 Aug;56:101580
pubmed: 34920941
Nat Rev Immunol. 2006 Aug;6(8):595-601
pubmed: 16868550
Nanoscale Horiz. 2022 Jun 27;7(7):682-714
pubmed: 35662310
Nat Biotechnol. 2018 Sep;36(8):707-716
pubmed: 29985479
Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):E6129-38
pubmed: 26504197
Nat Mater. 2012 Oct;11(10):895-905
pubmed: 22797827
Nat Nanotechnol. 2022 May;17(5):531-540
pubmed: 35410368
Acc Chem Res. 2019 May 21;52(5):1255-1264
pubmed: 30977635
Adv Mater. 2019 Apr;31(17):e1808294
pubmed: 30848011
Nat Commun. 2018 Jan 2;9(1):6
pubmed: 29295974
Nature. 2015 Oct 1;526(7571):118-21
pubmed: 26374997
Adv Healthc Mater. 2021 Mar;10(6):e2002081
pubmed: 33586322
Nat Rev Immunol. 2022 Oct;22(10):614-628
pubmed: 35217787
J Control Release. 2022 Sep;349:679-698
pubmed: 35878728
Trends Pharmacol Sci. 2012 Jan;33(1):35-41
pubmed: 22032984
J Immunother Cancer. 2020 Nov;8(2):
pubmed: 33203664
Nat Biomed Eng. 2018 Jun;2(6):341-346
pubmed: 30116654
Adv Mater. 2022 Mar;34(9):e2106516
pubmed: 34962660
Nat Immunol. 2012 Dec;13(12):1141-2
pubmed: 23160210
J Am Chem Soc. 2014 Sep 3;136(35):12296-303
pubmed: 25116377
Nat Mater. 2017 Apr;16(4):489-496
pubmed: 28024156
Nat Rev Immunol. 2017 Jan;17(1):30-48
pubmed: 27890914
Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):599-608
pubmed: 30587590
J Clin Invest. 2014 Jan;124(1):99-110
pubmed: 24292706
Nat Commun. 2016 Oct 21;7:13193
pubmed: 27767031
Adv Mater. 2020 Apr;32(13):e1901255
pubmed: 31206841
Nature. 2011 Mar 31;471(7340):629-32
pubmed: 21455179
Immunity. 2013 Jan 24;38(1):13-25
pubmed: 23352221
Nat Commun. 2019 May 2;10(1):2025
pubmed: 31048681