Promoting antigen escape from dendritic cell endosomes potentiates anti-tumoral immunity.
Accum
anti-tumoral immunity
antigen cross-presentation
dendritic cells
endosomes
immune checkpoint inhibitors
tumor-infiltrating lymphocytes
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
15 03 2022
15 03 2022
Historique:
received:
11
06
2021
revised:
17
12
2021
accepted:
27
01
2022
entrez:
2
5
2022
pubmed:
3
5
2022
medline:
4
5
2022
Statut:
epublish
Résumé
The cross-presenting capacity of dendritic cells (DCs) can be limited by non-specific degradation during endosome maturation. To bypass this limitation, we present in this study a new Accum-based formulation designed to promote endosome-to-cytosol escape. Treatment of primary DCs with Accum linked to the xenoantigen ovalbumin (OVA) triggers endosomal damages and enhances protein processing. Despite multiple challenges using ascending doses of tumor cells, DC prophylactic vaccination results in complete protection due to increased levels of effector CD4 and CD8 T cells as well as high production of pro-inflammatory mediators. When combined with anti-PD-1, therapeutic vaccination using both syngeneic and allogeneic Accum-OVA-pulsed DCs triggers potent anti-tumoral responses. The net outcome culminates in increased CD11c, CD8, and NK infiltration along with a high CD8/Treg ratio. These highly favorable therapeutic effects highlight the promising potential of Accum as a distinct and potent technology platform suitable for the design of next generation cell cancer vaccines.
Identifiants
pubmed: 35492876
doi: 10.1016/j.xcrm.2022.100534
pii: S2666-3791(22)00034-9
pmc: PMC9040180
doi:
Substances chimiques
Cancer Vaccines
0
Ovalbumin
9006-59-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100534Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
S.B. and S.P. are current employees of Defence Therapeutics Inc. and declare competing financial interest.
Références
Sci Rep. 2016 Feb 24;6:22064
pubmed: 26907999
Science. 2011 Mar 25;331(6024):1565-70
pubmed: 21436444
Science. 2005 Mar 11;307(5715):1630-4
pubmed: 15761154
Nat Med. 2004 May;10(5):475-80
pubmed: 15122249
J Immunol. 2000 Oct 1;165(7):3730-41
pubmed: 11034378
Cancer Immunol Immunother. 2020 Nov;69(11):2393-2401
pubmed: 32535637
J Immunol. 2009 Mar 15;182(6):3335-41
pubmed: 19265109
Cell Microbiol. 2010 Apr 1;12(4):530-44
pubmed: 19951367
Cell. 2006 Jul 14;126(1):205-18
pubmed: 16839887
J Cell Biol. 2013 Oct 14;203(1):115-28
pubmed: 24100292
Dev Cell. 2020 Jan 6;52(1):69-87.e8
pubmed: 31813797
Front Immunol. 2014 Apr 17;5:176
pubmed: 24860566
Science. 2003 Feb 28;299(5611):1400-3
pubmed: 12610307
Oncoimmunology. 2017 Nov 27;7(3):e1395126
pubmed: 29399392
Blood. 2008 Dec 1;112(12):4712-22
pubmed: 18682599
Mol Pharm. 2016 Jun 6;13(6):1915-26
pubmed: 27112376
Gene Ther. 2012 Oct;19(10):1035-40
pubmed: 22071967
Cell Rep. 2020 Jul 14;32(2):107905
pubmed: 32668257
Lancet Oncol. 2014 Jun;15(7):e257-67
pubmed: 24872109
Science. 2018 Apr 6;360(6384):
pubmed: 29622626
Cell Immunol. 1999 Jun 15;194(2):143-9
pubmed: 10383817
Dev Cell. 2017 Apr 10;41(1):10-22
pubmed: 28399394
Dev Cell. 2016 Oct 10;39(1):13-27
pubmed: 27693506
Annu Rev Immunol. 2018 Apr 26;36:717-753
pubmed: 29490164
Immunity. 2009 Apr 17;30(4):544-55
pubmed: 19328020
J Immunol. 2010 Aug 1;185(3):1361-6
pubmed: 20660360
Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10729-34
pubmed: 16807294
Nat Cell Biol. 1999 Oct;1(6):362-8
pubmed: 10559964
Nat Cell Biol. 2007 Apr;9(4):367-78
pubmed: 17351642
Nat Commun. 2019 Nov 27;10(1):5408
pubmed: 31776331
Immunity. 2015 May 19;42(5):850-63
pubmed: 25979419
J Immunol. 2010 Aug 1;185(3):1353-4
pubmed: 20660358
EMBO J. 2012 Feb 15;31(4):932-44
pubmed: 22157818
Ann Transl Med. 2016 Jul;4(14):266
pubmed: 27563653
Oncoimmunology. 2017 Dec 26;7(3):e1397250
pubmed: 29399398
Proc Natl Acad Sci U S A. 2005 May 31;102(22):7922-7
pubmed: 15894616