Evaluation of cyclin A1-specific T cells as a potential treatment for acute myeloid leukemia.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
28 Jan 2020
28 Jan 2020
Historique:
received:
17
07
2019
accepted:
01
12
2019
entrez:
28
1
2020
pubmed:
28
1
2020
medline:
21
7
2020
Statut:
ppublish
Résumé
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for relapsed or refractory acute myeloid leukemia (AML). However, more than half ultimately experience disease relapse that is associated with a dismal median survival of just 6 months, highlighting the need for novel therapies. In the current study we explore the therapeutic potential of targeting cyclin A1 (CCNA1), a cancer-testis antigen that is overexpressed in malignant blasts and leukemic stem cells. We demonstrate the immunogenicity of this antigen to native T cells, with >90% of donors screened mounting a specific response. The expanded cells were Th1 polarized, polyfunctional, and cytotoxic toward CCNA1+/HLA-matched tumor cell lines. Furthermore, these cells were exquisitely specific for CCNA1 and exhibited no reactivity against other cyclin family members, including CCNA2, which shares 56% homology with CCNA1 and is ubiquitously expressed in dividing cells. Lastly, the detection of CCNA1-specific T cells in AML patients post-HSCT was associated with prolonged disease remission, suggesting the protective potential of such endogenous cells. Taken together, our findings demonstrate the feasibility of targeting CCNA1 and the potential for therapeutic benefit associated with the adoptive transfer of reactive cells.
Identifiants
pubmed: 31985805
pii: S2473-9529(20)31668-2
doi: 10.1182/bloodadvances.2019000715
pmc: PMC6988407
doi:
Substances chimiques
CCNA1 protein, human
0
Cyclin A1
0
Types de publication
Evaluation Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
387-397Subventions
Organisme : NCI NIH HHS
ID : P50 CA126752
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
Références
J Clin Oncol. 1997 Feb;15(2):433-44
pubmed: 9053463
Blood Cancer J. 2016 Jul 01;6(7):e441
pubmed: 27367478
Blood Cancer J. 2014 Jun 13;4:e218
pubmed: 24927407
Biol Blood Marrow Transplant. 2015 Mar;21(3):454-9
pubmed: 25460355
Blood. 2017 Aug 10;130(6):722-731
pubmed: 28588020
Cancer Treat Rev. 2010 Nov;36(7):528-38
pubmed: 20381970
Sci Transl Med. 2013 Feb 27;5(174):174ra27
pubmed: 23447018
Clin Cancer Res. 2018 Nov 15;24(22):5502-5515
pubmed: 29903894
Cancer Res. 1997 Mar 1;57(5):913-20
pubmed: 9041194
Semin Hematol. 2019 Apr;56(2):155-163
pubmed: 30926092
Blood. 2001 Apr 1;97(7):2091-7
pubmed: 11264176
Blood. 2012 Jun 7;119(23):5492-501
pubmed: 22529286
Leukemia. 2012 Oct;26(10):2186-96
pubmed: 22652755
Arch Pathol Lab Med. 2015 Oct;139(10):1215-23
pubmed: 26414465
Clin Cancer Res. 2013 Sep 15;19(18):5079-91
pubmed: 23838315
Cancer Lett. 2003 Feb 10;190(1):89-95
pubmed: 12536081
Hematol Oncol Stem Cell Ther. 2017 Dec;10(4):245-251
pubmed: 28666104
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6853-8
pubmed: 11381140
Nat Rev Cancer. 2005 Aug;5(8):615-25
pubmed: 16034368
Eur J Haematol. 2005 Aug;75(2):106-15
pubmed: 16004607
Leukemia. 2015 Apr;29(4):770-5
pubmed: 25005246
Mol Ther. 2011 Dec;19(12):2258-68
pubmed: 21915103
J Immunol. 2018 Jan 15;200(2):459-468
pubmed: 29311388
Leuk Lymphoma. 2019 Jun;60(6):1370-1380
pubmed: 30628504
Am J Hematol. 2018 Jun 15;:
pubmed: 29905379
Leukemia. 2007 Jan;21(1):66-71
pubmed: 17051246
BMC Cancer. 2015 Oct 24;15:784
pubmed: 26499264
Genes Chromosomes Cancer. 2008 Jan;47(1):8-20
pubmed: 17910043
Blood. 2012 Feb 9;119(6):1599-606
pubmed: 22167752
Blood. 2009 Apr 30;113(18):4179-87
pubmed: 19008455
Br J Haematol. 2018 Apr;181(1):27-37
pubmed: 29318584
Oncogene. 2005 Apr 14;24(16):2739-44
pubmed: 15829981
Blood. 2018 Jan 4;131(1):121-130
pubmed: 29038338
J Clin Oncol. 2007 Nov 1;25(31):4938-45
pubmed: 17909197
Int J Oncol. 2009 Jan;34(1):129-36
pubmed: 19082485
Leukemia. 2014 May;28(5):1167-70
pubmed: 24472813
Int J Cancer. 2007 Aug 15;121(4):706-13
pubmed: 17455244
Eur J Immunol. 2013 Nov;43(11):2797-809
pubmed: 24258910
Nat Rev Mol Cell Biol. 2008 Nov;9(11):910-6
pubmed: 18813291
Blood. 2016 Jan 7;127(1):62-70
pubmed: 26660427
Int J Hematol. 2012 Aug;96(2):164-70
pubmed: 22791508
Oncol Lett. 2019 Jul;18(1):706-712
pubmed: 31289545
J Clin Oncol. 2011 Jul 10;29(20):2758-65
pubmed: 21632498
Blood. 2013 Aug 8;122(6):863-71
pubmed: 23770775
N Engl J Med. 2018 Jun 21;378(25):2386-2398
pubmed: 29860938
Clin Lab Med. 2017 Dec;37(4):753-769
pubmed: 29128067
Leukemia. 1998 Jun;12(6):893-8
pubmed: 9639417