Reconstitution of EBV-directed T cell immunity by adoptive transfer of peptide-stimulated T cells in a patient after allogeneic stem cell transplantation for AITL.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
16
12
2021
accepted:
31
03
2022
revised:
04
05
2022
pubmed:
23
4
2022
medline:
7
5
2022
entrez:
22
4
2022
Statut:
epublish
Résumé
Reconstitution of the T cell repertoire after allogeneic stem cell transplantation is a long and often incomplete process. As a result, reactivation of Epstein-Barr virus (EBV) is a frequent complication that may be treated by adoptive transfer of donor-derived EBV-specific T cells. We generated donor-derived EBV-specific T cells by stimulation with peptides representing defined epitopes covering multiple HLA restrictions. T cells were adoptively transferred to a patient who had developed persisting high titers of EBV after allogeneic stem cell transplantation for angioimmunoblastic T-cell lymphoma (AITL). T cell receptor beta (TCRβ) deep sequencing showed that the T cell repertoire of the patient early after transplantation (day 60) was strongly reduced and only very low numbers of EBV-specific T cells were detectable. Manufacturing and in vitro expansion of donor-derived EBV-specific T cells resulted in enrichment of EBV epitope-specific, HLA-restricted T cells. Monitoring of T cell clonotypes at a molecular level after adoptive transfer revealed that the dominant TCR sequences from peptide-stimulated T cells persisted long-term and established an EBV-specific TCR clonotype repertoire in the host, with many of the EBV-specific TCRs present in the donor. This reconstituted repertoire was associated with immunological control of EBV and with lack of further AITL relapse.
Identifiants
pubmed: 35452490
doi: 10.1371/journal.ppat.1010206
pii: PPATHOGENS-D-21-02534
pmc: PMC9067708
doi:
Substances chimiques
Epitopes
0
Peptides
0
Peptide T
106362-33-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010206Déclaration de conflit d'intérêts
I have read the journal’s policy and the authors of this manuscript have the following competing interests: AMo receives project funding from Biosyngen Pte. Ltd. for preclinical development of EBV-specific TCRs not related to this study.
Références
J Virol. 2006 Nov;80(21):10357-64
pubmed: 17041216
Curr Opin Oncol. 2014 Nov;26(6):677-83
pubmed: 25162331
Br J Cancer. 2018 Feb 20;118(4):534-545
pubmed: 29360818
Int J Hematol. 2019 Apr;109(4):499-504
pubmed: 30604313
Nat Med. 2013 Mar;19(3):372-7
pubmed: 23435170
Biol Blood Marrow Transplant. 2009 Jul;15(7):795-803
pubmed: 19539210
PLoS Pathog. 2012 Sep;8(9):e1002889
pubmed: 23028307
Infection. 2008 Mar;36(2):158-62
pubmed: 18379728
Blood. 2010 Apr 8;115(14):2960-70
pubmed: 20103780
Blood. 2010 Feb 4;115(5):925-35
pubmed: 19880495
Br J Haematol. 2019 Oct;187(2):206-218
pubmed: 31219185
Eur J Immunol. 2004 Sep;34(9):2500-9
pubmed: 15307182
Haematologica. 2016 Jul;101(7):803-11
pubmed: 27365460
Cancer Res. 2012 Mar 1;72(5):1116-25
pubmed: 22282657
Bone Marrow Transplant. 2020 Sep;55(9):1754-1762
pubmed: 32066862
Cytotherapy. 2019 Sep;21(9):935-942
pubmed: 31320195
J Exp Med. 2006 Apr 17;203(4):995-1006
pubmed: 16549597
Blood. 1992 Oct 1;80(7):1804-12
pubmed: 1327284
Clin Case Rep. 2021 May 05;9(5):e04083
pubmed: 34084501
PLoS Pathog. 2014 Aug 28;10(8):e1004333
pubmed: 25165855
Oncoimmunology. 2021 Aug 2;10(1):1955545
pubmed: 34377592
J Transl Med. 2018 May 9;16(1):124
pubmed: 29743075
Molecules. 2019 Mar 12;24(5):
pubmed: 30871092
Blood. 2003 Jun 1;101(11):4290-7
pubmed: 12576337
Hematol Oncol. 2020 Aug;38(3):272-276
pubmed: 32083758
Biol Blood Marrow Transplant. 2004 Mar;10(3):143-55
pubmed: 14993880
Nature. 1999 Oct 14;401(6754):708-12
pubmed: 10537110
Int J Cancer. 2002 May 1;99(1):93-9
pubmed: 11948498
J Cell Biol. 1991 Jul;114(2):343-9
pubmed: 1712790
J Clin Exp Hematop. 2010;50(1):59-63
pubmed: 20505277
J Exp Med. 1997 May 5;185(9):1605-17
pubmed: 9151898
Ther Adv Hematol. 2020 Apr 28;11:2040620720910964
pubmed: 32523657
Curr Top Microbiol Immunol. 2001;258:221-9
pubmed: 11443864
J Virol. 2001 Sep;75(18):8649-59
pubmed: 11507210
Am J Transplant. 2015 Aug;15(8):2170-9
pubmed: 25873100
Clin Infect Dis. 2006 Jun 15;42(12):1743-8
pubmed: 16705581
J Immunol. 2000 Nov 1;165(9):4831-41
pubmed: 11046006
Blood. 2002 Dec 1;100(12):4059-66
pubmed: 12393655
Nat Rev Clin Oncol. 2012 Sep;9(9):510-9
pubmed: 22801669
Blood. 2001 Aug 15;98(4):972-8
pubmed: 11493441
Leukemia. 2003 Dec;17(12):2257-317
pubmed: 14671650
J Biol Chem. 2007 Aug 17;282(33):23799-810
pubmed: 17540778
Blood. 1992 Apr 1;79(7):1789-95
pubmed: 1373088
J Immunol. 1999 Feb 1;162(3):1827-35
pubmed: 9973448
J Clin Invest. 2020 Feb 3;130(2):733-747
pubmed: 31689242
Blood. 2004 Feb 15;103(4):1408-16
pubmed: 14563644
Br J Haematol. 2007 Jul;138(1):44-53
pubmed: 17555446
Bone Marrow Transplant. 2013 Nov;48(11):1465-71
pubmed: 23749107
J Am Acad Dermatol. 2019 Oct;81(4):989-997
pubmed: 30240776
Bone Marrow Transplant. 2020 Jan;55(1):25-39
pubmed: 31089285
Annu Rev Immunol. 1997;15:405-31
pubmed: 9143694
Cancer Cell. 2014 Oct 13;26(4):565-76
pubmed: 25220446
PLoS One. 2013 Oct 25;8(10):e78686
pubmed: 24205294
J Virol. 1993 Dec;67(12):7428-35
pubmed: 7693972
J Clin Invest. 2005 Sep;115(9):2546-55
pubmed: 16110323
J Immunother Cancer. 2021 Jul;9(7):
pubmed: 34210819
J Exp Med. 1995 Jun 1;181(6):2221-8
pubmed: 7539044
Ann Transl Med. 2015 Apr;3(5):62
pubmed: 25992361
Hematol Rep. 2017 Sep 27;9(3):7088
pubmed: 29071053
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10391-6
pubmed: 10468618
J Virol. 1995 Aug;69(8):4872-9
pubmed: 7609055
Biol Blood Marrow Transplant. 2017 Sep;23(9):1437-1446
pubmed: 28495643
Cancer Med. 2020 Jan;9(2):678-688
pubmed: 31793218
J Gen Virol. 1994 Sep;75 ( Pt 9):2489-93
pubmed: 7521394
J Clin Oncol. 2013 Jan 1;31(1):39-48
pubmed: 23169501
J Exp Med. 1996 Nov 1;184(5):1791-800
pubmed: 8920867
J Immunol. 2005 Sep 15;175(6):3826-34
pubmed: 16148129
Blood. 2014 Oct 16;124(16):2514-22
pubmed: 25185261
PLoS Pathog. 2014 May 22;10(5):e1004068
pubmed: 24853673
Antivir Ther. 2004 Jun;9(3):453-9
pubmed: 15259909
Int Immunol. 2006 Apr;18(4):591-601
pubmed: 16507598
J Immunol. 2002 Aug 15;169(4):2172-9
pubmed: 12165547
Science. 1992 Jul 10;257(5067):238-41
pubmed: 1352912
Hum Gene Ther. 2021 Sep;32(17-18):919-935
pubmed: 33798008
BMC Immunol. 2021 Sep 28;22(1):65
pubmed: 34583647
Front Immunol. 2018 Oct 04;9:2291
pubmed: 30337929
J Immunol. 2011 Jun 15;186(12):7039-49
pubmed: 21555537
Eur J Immunol. 2000 Sep;30(9):2531-9
pubmed: 11009086