title: Chimeric antigen receptors and bispecific antibodies to retarget T cells in pediatric oncology.
abstract: Cancer immunotherapy using antigen-specific T cells has broad therapeutic potential. Chimeric antigen receptors and bispecific antibodies can redirect T cells to kill tumors without human leukocyte antigens (HLA) restriction. Key determinants of clinical potential include the choice of target antigen, antibody specificity, antibody affinity, tumor accessibility, T cell persistence, and tumor immune evasion. For pediatric cancers, additional constraints include their propensity for bulky metastatic disease and the concern for late toxicities from treatment. Nonetheless, the recent preclinical and clinical developments of these T cell based therapies are highly encouraging.
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, NY.
authors.forename: Maya
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, NY.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Curran
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, NY.
authors.forename: Nai-Kong V
authors.initials: NK
authors.lastname: Cheung
mesh_terms: D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002648:Child; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: T cells; bispecific antibodies; chimeric antigen receptors; immunotherapy; pediatric oncology
references.citation: Trends Pharmacol Sci. 2012 Jan;33(1):35-41
references.pmid: 22032984
references.citation: J Immunother. 2010 Jan;33(1):1-7
references.pmid: 19952961
references.citation: FEBS Lett. 2014 Jan 21;588(2):368-76
references.pmid: 24161671
references.citation: Nat Clin Pract Oncol. 2006 Dec;3(12):668-81
references.pmid: 17139318
references.citation: Blood. 2012 May 3;119(18):4133-41
references.pmid: 22354001
references.citation: Blood. 2014 Jul 10;124(2):188-95
references.pmid: 24876563
references.citation: Best Pract Res Clin Haematol. 2011 Sep;24(3):467-76
references.pmid: 21925100
references.citation: Cancer Res. 2012 Jan 1;72(1):24-32
references.pmid: 22044753
references.citation: Pharmacol Ther. 2015 Jun;150:23-32
references.pmid: 25583297
references.citation: Cancer Biother Radiopharm. 2010 Feb;25(1):13-9
references.pmid: 20187792
references.citation: Curr Opin Immunol. 2014 Apr;27:1-7
references.pmid: 24413387
references.citation: J Immunol. 1998 Sep 15;161(6):2791-7
references.pmid: 9743337
references.citation: Proc R Soc Med. 1910;3(Surg Sect):1-48
references.pmid: 19974799
references.citation: Pediatr Blood Cancer. 2012 Dec 15;59(7):1198-205
references.pmid: 22707078
references.citation: N Engl J Med. 2014 Oct 16;371(16):1507-17
references.pmid: 25317870
references.citation: Br Med J. 1957 Apr 6;1(5022):779-86
references.pmid: 13404306
references.citation: Cancer Res. 2014 Dec 1;74(23):6796-805
references.pmid: 25297631
references.citation: Mol Cancer Ther. 2012 Dec;11(12):2664-73
references.pmid: 23041545
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2493-8
references.pmid: 21576633
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17469-74
references.pmid: 19805141
references.citation: Sci Transl Med. 2014 Feb 19;6(224):224ra25
references.pmid: 24553386
references.citation: J Clin Invest. 2008 Jan;118(1):294-305
references.pmid: 18060041
references.citation: J Immunol. 2004 Dec 15;173(12):7647-53
references.pmid: 15585893
references.citation: Int J Cancer. 2015 Jan 15;136(2):476-86
references.pmid: 24895182
references.citation: Oncoimmunology. 2015 Apr 27;4(4):e989776
references.pmid: 26137406
references.citation: Int J Cancer. 2005 Nov 10;117(3):435-43
references.pmid: 15906359
references.citation: Mol Ther. 2010 Nov;18(11):2006-17
references.pmid: 20842106
references.citation: Cancer Res. 2011 Apr 15;71(8):2871-81
references.pmid: 21487038
references.citation: Mol Cancer Ther. 2014 Jul;13(7):1803-12
references.pmid: 24944121
references.citation: Cancer Res. 2006 Nov 15;66(22):10995-1004
references.pmid: 17108138
references.citation: Mol Ther. 2010 Apr;18(4):843-51
references.pmid: 20179677
references.citation: Science. 2011 Mar 25;331(6024):1565-70
references.pmid: 21436444
references.citation: Front Immunol. 2014 Oct 07;5:489
references.pmid: 25339957
references.citation: Nature. 1985 Apr 18-24;314(6012):628-31
references.pmid: 2859527
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: J Immunol. 2004 Dec 15;173(12):7125-30
references.pmid: 15585832
references.citation: Cancer. 2007 Jan 15;109(2):170-9
references.pmid: 17154393
references.citation: N Engl J Med. 2013 Apr 18;368(16):1509-18
references.pmid: 23527958
references.citation: Blood. 2009 Jun 18;113(25):6392-402
references.pmid: 19377047
references.citation: J Immunother. 2008 Nov-Dec;31(9):812-9
references.pmid: 18833006
references.citation: J Clin Invest. 1959 Oct;38:1709-16
references.pmid: 13837954
references.citation: Cancer Res. 2009 Jun 15;69(12):4941-4
references.pmid: 19509221
references.citation: J Gene Med. 2012 Jun;14(6):405-15
references.pmid: 22262649
references.citation: Blood. 2007 Mar 1;109(5):2014-22
references.pmid: 17062729
references.citation: MAbs. 2012 Mar-Apr;4(2):182-97
references.pmid: 22453100
references.citation: Lancet. 2015 Feb 7;385(9967):517-28
references.pmid: 25319501
references.citation: Clin Cancer Res. 2012 May 15;18(10):2780-90
references.pmid: 22589486
references.citation: Blood. 2012 Jan 19;119(3):696-706
references.pmid: 22117050
references.citation: Pediatr Blood Cancer. 2014 Mar;61(3):452-6
references.pmid: 23956055
references.citation: Oncoimmunology. 2012 Sep 1;1(6):863-873
references.pmid: 23162754
references.citation: Nature. 1983 Oct 6-12;305(5934):537-40
references.pmid: 6137772
references.citation: Clin Pharmacol. 2013 Apr 12;5(Suppl 1):5-11
references.pmid: 23671399
references.citation: Nat Rev Cancer. 2012 Mar 22;12(4):278-87
references.pmid: 22437872
references.citation: Angiogenesis. 2011 Sep;14 (3):255-66
references.pmid: 21484514
references.citation: J Immunol. 2001 Dec 1;167(11):6123-31
references.pmid: 11714771
references.citation: Blood. 2012 Jun 28;119(26):6226-33
references.pmid: 22592608
references.citation: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6106-15
references.pmid: 17062687
references.citation: Cancer Immunol Res. 2015 Mar;3(3):266-77
references.pmid: 25542634
references.citation: Semin Oncol. 2014 Apr;41(2):174-84
references.pmid: 24787291
references.citation: Gene Ther. 2005 Jun;12(12):999-1010
references.pmid: 15789061
references.citation: Hum Gene Ther. 2010 Jan;21(1):75-86
references.pmid: 19719389
references.citation: Blood. 2011 Dec 1;118(23):6050-6
references.pmid: 21984804
references.citation: Carcinogenesis. 2005 Dec;26(12):2105-15
references.pmid: 16051641
references.citation: Hum Gene Ther. 2002 Nov 1;13(16):1971-80
references.pmid: 12427307
references.citation: Cancer Res. 2014 Oct 1;74(19):5561-71
references.pmid: 25228655
references.citation: Annu Rev Immunol. 2012;30:531-64
references.pmid: 22224781
references.citation: Blood. 2013 Feb 14;121(7):1165-74
references.pmid: 23243285
references.citation: Blood. 2005 Jan 15;105(2):865-73
references.pmid: 15280205
references.citation: Mol Ther. 2011 Apr;19(4):760-7
references.pmid: 21326215
references.citation: Nat Rev Cancer. 2013 Jun;13(6):397-411
references.pmid: 23702928
references.citation: Nat Med. 2008 Nov;14(11):1264-70
references.pmid: 18978797
references.citation: Front Oncol. 2012 Jan 30;2:3
references.pmid: 22645714
references.citation: Blood. 2012 Apr 26;119(17):3940-50
references.pmid: 22308288
references.citation: Future Oncol. 2013 Apr;9(4):527-39
references.pmid: 23560375
references.citation: J Transl Med. 2014 Jul 09;12 :191
references.pmid: 25008236
references.citation: MAbs. 2009 Nov-Dec;1(6):539-47
references.pmid: 20073127
references.citation: Oncoimmunology. 2013 Dec 1;2(12):e26757
references.pmid: 24475376
references.citation: Cancer Res. 2007 Jan 1;67(1):57-65
references.pmid: 17210683
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7021-5
references.pmid: 7624362
references.citation: Clin Cancer Res. 2007 Jul 1;13(13):3899-905
references.pmid: 17606723