CD123 as a Therapeutic Target in the Treatment of Hematological Malignancies.
acute myeloid leukemia
biomarker
interleukin-3
interleukin-3 receptor
leukemia
leukemic stem cells
therapy
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
12 Sep 2019
12 Sep 2019
Historique:
received:
14
08
2019
revised:
08
09
2019
accepted:
09
09
2019
entrez:
25
9
2019
pubmed:
25
9
2019
medline:
25
9
2019
Statut:
epublish
Résumé
The interleukin-3 receptor alpha chain (IL-3R), more commonly referred to as CD123, is widely overexpressed in various hematological malignancies, including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, Hodgkin lymphoma and particularly, blastic plasmacytoid dendritic neoplasm (BPDCN). Importantly, CD123 is expressed at both the level of leukemic stem cells (LSCs) and more differentiated leukemic blasts, which makes CD123 an attractive therapeutic target. Various agents have been developed as drugs able to target CD123 on malignant leukemic cells and on the normal counterpart. Tagraxofusp (SL401, Stemline Therapeutics), a recombinant protein composed of a truncated diphtheria toxin payload fused to IL-3, was approved for use in patients with BPDCN in December of 2018 and showed some clinical activity in AML. Different monoclonal antibodies directed against CD123 are under evaluation as antileukemic drugs, showing promising results either for the treatment of AML minimal residual disease or of relapsing/refractory AML or BPDCN. Finally, recent studies are exploring T cell expressing CD123 chimeric antigen receptor-modified T-cells (CAR T) as a new immunotherapy for the treatment of refractory/relapsing AML and BPDCN. In December of 2018, MB-102 CD123 CAR T developed by Mustang Bio Inc. received the Orphan Drug Designation for the treatment of BPDCN. In conclusion, these recent studies strongly support CD123 as an important therapeutic target for the treatment of BPDCN, while a possible in the treatment of AML and other hematological malignancies will have to be evaluated by in the ongoing clinical studies.
Identifiants
pubmed: 31547472
pii: cancers11091358
doi: 10.3390/cancers11091358
pmc: PMC6769702
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Haematologica. 2011 Dec;96(12):1792-8
pubmed: 21933861
Leukemia. 2000 Oct;14(10):1777-84
pubmed: 11021753
Cancer Discov. 2019 Aug;9(8):1050-1063
pubmed: 31088841
N Engl J Med. 2018 Feb 1;378(5):439-448
pubmed: 29385370
Cell Rep. 2014 Jul 24;8(2):410-9
pubmed: 25043189
Haematologica. 2015 Feb;100(2):223-30
pubmed: 25381130
J Clin Invest. 2016 Oct 3;126(10):3814-3826
pubmed: 27571406
Blood. 2014 Feb 20;123(8):1218-28
pubmed: 24363400
Cytometry B Clin Cytom. 2019 Mar;96(2):134-142
pubmed: 30450744
Blood Cancer J. 2017 Jun 2;7(6):e567
pubmed: 28574487
Blood. 2017 Feb 2;129(5):553-560
pubmed: 27903528
Br J Haematol. 2014 Sep;166(6):862-74
pubmed: 24942980
Leukemia. 2018 Jun;32(6):1317-1326
pubmed: 29515236
Leukemia. 2019 Jan;33(1):64-74
pubmed: 29946192
Blood. 2015 Feb 26;125(9):1367-76
pubmed: 25550361
Blood. 2011 Jun 9;117(23):6267-76
pubmed: 21487112
N Engl J Med. 2018 Mar 29;378(13):1189-1199
pubmed: 29601269
Haematologica. 2009 Jul;94(7):1016-9
pubmed: 19454491
Br J Haematol. 2013 May;161(3):389-401
pubmed: 23432359
J Clin Oncol. 2019 Feb 10;37(5):375-385
pubmed: 30403573
Haematologica. 2019 Apr;104(4):749-755
pubmed: 30361418
Protein Eng Des Sel. 2012 Oct;25(10):561-9
pubmed: 22740616
Mol Ther. 2017 Aug 2;25(8):1933-1945
pubmed: 28479045
Leuk Lymphoma. 2008 Mar;49(3):543-53
pubmed: 18297533
Cell. 2012 Jul 20;150(2):264-78
pubmed: 22817890
Cancer Immunol Immunother. 2005 Aug;54(8):799-806
pubmed: 15614527
Nat Med. 2019 Apr;25(4):603-611
pubmed: 30911134
Blood. 2001 May 15;97(10):3210-7
pubmed: 11342451
Nat Genet. 2017 Feb;49(2):204-212
pubmed: 27992414
Blood Cancer J. 2014 Jun 13;4:e218
pubmed: 24927407
Nature. 2017 Jul 6;547(7661):104-108
pubmed: 28658204
N Engl J Med. 2016 Feb 4;374(5):422-33
pubmed: 26789727
Blood Adv. 2016 Dec 14;1(3):193-204
pubmed: 29296935
Oncoimmunology. 2018 Jul 30;7(9):e1472195
pubmed: 30228941
Leukemia. 2019 May;33(5):1113-1123
pubmed: 30568172
Haematologica. 2015 Jul;100(7):914-26
pubmed: 26130514
Blood. 2006 Nov 15;108(10):3530-7
pubmed: 16882709
J Clin Invest. 1993 Jun;91(6):2887-92
pubmed: 7685775
Int J Mol Sci. 2019 Jan 08;20(1):null
pubmed: 30626126
Blood. 2014 Jul 17;124(3):385-92
pubmed: 24859366
Cancers (Basel). 2019 Apr 28;11(5):null
pubmed: 31035408
Blood. 2014 Apr 10;123(15):2343-54
pubmed: 24596416
Blood. 2019 Mar 7;133(10):1140-1151
pubmed: 30610028
Clin Cancer Res. 2017 Jul 1;23(13):3385-3395
pubmed: 28096272
JCI Insight. 2018 Mar 8;3(5):
pubmed: 29515031
Immunol Rev. 2012 Nov;250(1):277-302
pubmed: 23046136
Nat Commun. 2019 Mar 25;10(1):1065
pubmed: 30911002
Appl Immunohistochem Mol Morphol. 2013 May;21(3):212-7
pubmed: 22914610
Br J Haematol. 2011 Apr;153(1):33-42
pubmed: 21332708
Blood. 2013 Oct 31;122(18):3138-48
pubmed: 24030378
Biol Blood Marrow Transplant. 2011 Oct;17(10):1450-1459.e1
pubmed: 21781950
Haematologica. 2019 Aug;104(8):1521-1531
pubmed: 31366466
Blood Cancer J. 2019 Jan 16;9(2):7
pubmed: 30651532
J Clin Oncol. 2017 Mar 20;35(9):934-946
pubmed: 28297624
Clin Cancer Res. 2006 Feb 15;12(4):1284-91
pubmed: 16489085
Blood Adv. 2017 Jun 20;1(15):1067-1079
pubmed: 29296749
Haematologica. 2019 Jul;104(7):1302-1308
pubmed: 31221785
Clin Lymphoma Myeloma Leuk. 2019 Sep;19(9):545-554
pubmed: 31281107
Blood Adv. 2018 Jun 12;2(11):1356-1366
pubmed: 29895626
Am J Clin Pathol. 2011 Oct;136(4):625-30
pubmed: 21917686
Science. 2018 Mar 23;359(6382):1361-1365
pubmed: 29567707
J Clin Invest. 2019 Oct 14;:null
pubmed: 31437130
Genes Chromosomes Cancer. 2019 Dec;58(12):828-838
pubmed: 30939217
Int J Mol Sci. 2019 Feb 12;20(3):null
pubmed: 30759825
Cell Stem Cell. 2009 Jul 2;5(1):31-42
pubmed: 19570512
Clin Cancer Res. 2015 Sep 1;21(17):3977-85
pubmed: 25957287
Blood Cancer J. 2019 Jan 15;9(2):6
pubmed: 30647406
Blood. 1996 Oct 1;88(7):2458-64
pubmed: 8839836
Blood. 2019 Mar 21;133(12):1290-1297
pubmed: 30578254
Nat Commun. 2018 Jan 26;9(1):386
pubmed: 29374162
J Hematol Oncol. 2018 May 2;11(1):61
pubmed: 29720227
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Haematologica. 2013 Feb;98(2):239-46
pubmed: 23065521
Cytokine Growth Factor Rev. 2013 Jun;24(3):189-201
pubmed: 23535386
Blood. 2017 Apr 27;129(17):2395-2407
pubmed: 28246194
Leukemia. 2019 May;33(5):1102-1112
pubmed: 30542144
Leuk Res. 2013 Apr;37(4):401-409
pubmed: 23347903
Blood. 2005 Oct 1;106(7):2527-9
pubmed: 15928038
Int J Hematol. 2019 May;109(5):539-544
pubmed: 30847774
Cytometry B Clin Cytom. 2011 Mar;80(2):91-9
pubmed: 20809502
Blood. 2013 Jan 17;121(3):440-6
pubmed: 23203822
Nat Commun. 2019 May 2;10(1):2031
pubmed: 31048683
Immunol Rev. 2019 Jul;290(1):39-59
pubmed: 31355492
Leukemia. 2019 Apr;33(4):931-944
pubmed: 30291336
Am J Clin Pathol. 2009 Oct;132(4):573-80
pubmed: 19762535
Leukemia. 2004 Feb;18(2):219-26
pubmed: 14671644
Leukemia. 2014 Aug;28(8):1596-605
pubmed: 24504024
Sci Transl Med. 2015 May 27;7(289):289ra82
pubmed: 26019218
Leukemia. 2019 Feb;33(2):348-357
pubmed: 30089916
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
N Engl J Med. 2015 Sep 17;373(12):1136-52
pubmed: 26376137
Mod Pathol. 2019 Sep;32(9):1373-1385
pubmed: 31000771
Ann Intern Med. 1999 Oct 5;131(7):549-50
pubmed: 10507983
Oncotarget. 2018 Sep 25;9(75):34056-34065
pubmed: 30344921
Hum Gene Ther. 2017 Oct;28(10):897-913
pubmed: 28810809
J Clin Med. 2019 Feb 06;8(2):null
pubmed: 30736352
Blood. 2016 Jan 7;127(1):122-31
pubmed: 26531164
Haematologica. 2001 Dec;86(12):1261-9
pubmed: 11726317
Blood. 2016 Jan 7;127(1):62-70
pubmed: 26660427
Leuk Lymphoma. 2004 Aug;45(8):1647-56
pubmed: 15370220
Cytokine. 2015 Aug;74(2):247-58
pubmed: 25982846
Biomark Res. 2014 Feb 10;2(1):4
pubmed: 24513123
Growth Factors. 2012 Apr;30(2):63-75
pubmed: 22257375
J Natl Compr Canc Netw. 2017 Jul;15(7):926-957
pubmed: 28687581
Leukemia. 2019 Oct;33(10):2466-2480
pubmed: 30894665
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Blood. 2018 Jul 12;132(2):187-196
pubmed: 29692343
Clin Cancer Res. 2018 Apr 1;24(7):1716-1726
pubmed: 29330206
N Engl J Med. 2019 Apr 25;380(17):1628-1637
pubmed: 31018069
Blood. 1996 Jan 1;87(1):83-92
pubmed: 8547680
Blood Adv. 2018 Apr 24;2(8):848-858
pubmed: 29661755
Leukemia. 2019 Sep;33(9):2195-2207
pubmed: 30816327
Br J Haematol. 2009 Feb;144(3):376-87
pubmed: 19036083
Blood Adv. 2019 Jul 23;3(14):2199-2204
pubmed: 31324640
Leukemia. 2019 Jul;33(7):1635-1649
pubmed: 30692594
Clin Lymphoma Myeloma Leuk. 2019 Jul;19(7):e349-e358
pubmed: 31076372
Leukemia. 2014 Nov;28(11):2213-21
pubmed: 24705479
Haematologica. 2018 Dec;103(12):e581-e584
pubmed: 29954937
Blood. 2002 Oct 15;100(8):2980-8
pubmed: 12351411
Haematologica. 2004 Mar;89(3):303-8
pubmed: 15020268
J Hematol Oncol. 2016 Jul 27;9(1):61
pubmed: 27465508
Blood Cells Mol Dis. 2015 Dec;55(4):336-46
pubmed: 26460257
Chem Immunol. 1992;51:65-106
pubmed: 1567546
Leuk Lymphoma. 2015 May;56(5):1406-15
pubmed: 25248882
Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):37-44
pubmed: 29222235
Haematologica. 2018 Aug;103(8):1288-1297
pubmed: 29773600
Leukemia. 2000 Apr;14(4):576-85
pubmed: 10764142
Leukemia. 2019 Aug;33(8):2061-2077
pubmed: 30705411
Leukemia. 2017 Dec;31(12):2652-2660
pubmed: 28479592
N Engl J Med. 2018 Dec 13;379(24):2330-2341
pubmed: 30380364
Ann Hematol. 2012 Oct;91(10):1541-6
pubmed: 22669506
Blood. 2001 Oct 15;98(8):2301-7
pubmed: 11588023
Nature. 2012 Jan 11;481(7382):506-10
pubmed: 22237025
Nat Med. 2019 Jan;25(1):103-110
pubmed: 30510255
JCI Insight. 2018 May 3;3(9):
pubmed: 29720577