title: High sensitivity of cancer exome-based CD8 T cell neo-antigen identification.
abstract: Recent data suggest that T-cell reactivity against tumor-specific neo-antigens may be central to the clinical efficacy of cancer immunotherapy. The development of personalized vaccines designed to boost T-cell reactivity against patient specific neo-antigens has been proposed largely on the basis of these findings. Work from several groups has demonstrated that novel tumor-specific antigens can be discovered through the use of cancer exome sequencing data, thereby providing a potential pipeline for the development of patient-specific vaccines. Importantly though, it has not been established which fraction of cancer neo-antigens that can be recognized by CD8+T cells is successfully uncovered with the current exome-based epitope prediction strategies. Here, we use a data set comprising human cancer neo-antigens that was previously identified through the use of unbiased, computational-independent strategies to describe the potential of cancer exome-based neo-antigen discovery. This analysis shows a high sensitivity of exome-guided neo-antigen prediction of approximately 70%. We propose that future research should focus on the analysis and optimization of the specificity of neo-antigen prediction, and should undoubtedly entail the clinical evaluation of patient-specific vaccines with the aim of inducing immunoreactivity against tumor-displayed neo-antigens in a physiologically relevant context.
authors.affiliation: Department of Immunology; The Netherlands Cancer Institute; Amsterdam, The Netherlands.
authors.forename: Marit M
authors.initials: MM
authors.lastname: van Buuren
authors.affiliation: Department of Immunology; The Netherlands Cancer Institute; Amsterdam, The Netherlands.
authors.forename: Jorg Ja
authors.initials: JJ
authors.lastname: Calis
authors.affiliation: Department of Immunology; The Netherlands Cancer Institute; Amsterdam, The Netherlands.
authors.forename: Ton Nm
authors.initials: TN
authors.lastname: Schumacher
keywords: epitope prediction; immune monitoring; neo-antigens; tumor vaccine; whole exome sequencing
references.citation: Eur J Immunol. 1999 Feb;29(2):592-601
references.pmid: 10064075
references.citation: Nature. 2012 Feb 08;482(7385):400-4
references.pmid: 22318521
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16013-8
references.pmid: 16247014
references.citation: PLoS Comput Biol. 2012;8(3):e1002412
references.pmid: 22396638
references.citation: Oncoimmunology. 2014 Jan 1;3(1):e27817
references.pmid: 24605269
references.citation: Cancer Res. 2012 Mar 1;72(5):1081-91
references.pmid: 22237626
references.citation: Clin Cancer Res. 2014 Mar 1;20(5):1125-34
references.pmid: 24323902
references.citation: Nature. 2013 Aug 22;500(7463):415-21
references.pmid: 23945592
references.citation: BMC Bioinformatics. 2009 Nov 30;10:394
references.pmid: 19948066
references.citation: N Engl J Med. 2010 Aug 19;363(8):711-23
references.pmid: 20525992
references.citation: Science. 1995 Sep 1;269(5228):1281-4
references.pmid: 7652577
references.citation: Cancer Res. 2001 May 15;61(10):4078-83
references.pmid: 11358829
references.citation: J Immunother. 2005 Jan-Feb;28(1):53-62
references.pmid: 15614045
references.citation: J Immunol. 1998 Jun 15;160(12):6188-94
references.pmid: 9637538
references.citation: PLoS One. 2007 Aug 29;2(8):e796
references.pmid: 17726526
references.citation: Cancer Res. 2001 May 1;61(9):3718-24
references.pmid: 11325844
references.citation: Clin Cancer Res. 2010 Dec 15;16(24):6122-31
references.pmid: 20668005
references.citation: N Engl J Med. 2012 Jun 28;366(26):2443-54
references.pmid: 22658127
references.citation: Int J Cancer. 2006 Apr 15;118(8):1992-7
references.pmid: 16287085
references.citation: J Exp Med. 1996 Mar 1;183(3):1185-92
references.pmid: 8642260
references.citation: EMBO J. 2013 Jan 23;32(2):194-203
references.pmid: 23258224
references.citation: Protein Eng. 2002 Apr;15(4):287-96
references.pmid: 11983929
references.citation: Cancer Immunol Res. 2014 Jun;2(6):522-9
references.pmid: 24894089
references.citation: Cancer Res. 2005 Jan 15;65(2):632-40
references.pmid: 15695408
references.citation: J Immunol. 1999 Feb 1;162(3):1730-8
references.pmid: 9973436
references.citation: Nat Med. 2013 Jun;19(6):747-52
references.pmid: 23644516
references.citation: Cancer Res. 1998 Nov 15;58(22):5144-50
references.pmid: 9823325
references.citation: J Clin Oncol. 2013 Nov 10;31(32):e439-42
references.pmid: 24043743
references.citation: J Immunol. 2004 Feb 15;172(4):2324-31
references.pmid: 14764701
references.citation: N Engl J Med. 2013 Jul 11;369(2):122-33
references.pmid: 23724867
references.citation: J Immunol. 2000 Jun 1;164(11):6057-66
references.pmid: 10820291
references.citation: Cancer Res. 1999 Nov 15;59(22):5785-92
references.pmid: 10582700
references.citation: N Engl J Med. 2013 Jul 11;369(2):134-44
references.pmid: 23724846
references.citation: Clin Cancer Res. 2013 Oct 1;19(19):5300-9
references.pmid: 24089443