identifying patient-specific neoepitopes for cell-based and
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TCGA Barcode UCSC id HUGO Gene
Neoepitope Protein Change
Normal Cancers
TCGA-E2-A109, TCGA-CR-5249, TCGA-BA-6872, TCGA-CN-6989
uc001wxt.2 SOS2 YIHTHTFYV p.T390I YTHTHTFYV (3) HNSC,
BRCA
TCGA-EW-A1J5, TCGA-21-1082,
TCGA-GD-A2C5, TCGA-75-5147
uc001zyl.4 USP8 SQIWNLNPV p.R763W SQIRNLNPV
LUAD, BLCA, LUSC, BRCA
ENA 2016. Nov 29-Dec 2, 2016, Munich, Germany © 2016 NantOmics, LLC. All Rights Reserved.
Identifying Patient-specific Neoepitopes for Cell-based and Vaccine Immunotherapy within the Cancer Genome Atlas Reveals Rarely Shared Recurrent Neoepitopes
Abstract: ENA-0510
• TCGA WGS and RNASeq data were obtained from the University of California, Santa Cruz (UCSC) Cancer Genomics Hub (https://cghub.ucsc.edu/).
• Neoepitopes were identified by creating all possible permutations of either 9-mer or 15-mer amino acid strings derived from somatic single nucleotide variants (SNVs) or insertions/deletions (indels) in coding regions.
• Potential neoepitopes were filtered against all possible 9-mer and 15-mer sequences from reference human coding genes, in addition to all possible variation in dbSNP (http://www.ncbi.nlm.nih.gov/SNP) sites.
• In-silico HLA typing was performed using WGS and RNAseq data by alignment to the IMGT/HLA database. Typing results were obtained for HLA-A, HLA-B, HLA-C, and HLA-DRB1.
• NetMHC 3.4 (http://www.cbs.dtu.dk/services/NetMHC-3.4/) was used to predict MHC to neoepitope binding affinities.
• Nearly all identified neoepitopes are patient-specific. TNBC samples do not share any common neoepitopes.
• Neoepitope-MHC interactions restrict more commonly shared mutations.
• Development of personalized immunotherapies is dependent on accurate DNA and RNA sequencing.
• Immunotherapies such as checkpoint inhibitors, CAR T cells, NK cells, and therapeutic vaccines are revolutionizing cancer medicine with remarkable responses in some patients.
• Immune cells attack both cancer related antigens such as HER2 and unique cancer neoantigens derived from private mutations.
• Checkpoint inhibitors allow immune cells to attack neoantigen presenting cancer cells that have otherwise evaded the immune system.
• We analyzed whole genome sequencing (WGS) and RNA sequencing (RNAseq) data from The Cancer Genome Atlas (TCGA) to identify neoepitopes (tumor-specific antigens derived from somatic tumor mutations) that could be exploited to develop next-generation, patient-specific cancer immunotherapies.
Background
Methods
Results
Conclusions
Andy Nguyen,1 J Zachary Sanborn,1 Charles J Vaske,1 Shahrooz Rabizadeh,2 Kayvan Niazi,2 Patrick Soon-Shiong,2,3 Steven C Benz1
1NantOmics LLC, Santa Cruz, CA; 2NantOmics LLC, Culver City, CA; 3CSS Institute of Molecular Medicine, Culver City, CA
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Clonality of Neoepitopes across cancer classifications
Filtering High-Quality Neoepitopes in HER2+ BRCA
TCGA Barcode UCSC id HUGO Gene TPM Neoepitope
Protein Change Normal
Bound Allele
Bind Strength
TCGA-BH-A18R uc003ean.2 FANCD2
21.39 FAKDGGLVT P714L FAKDGGPVT
C*03:03 131nM
TCGA-AO-A0JM 14.12 C*05:01 851nM
A Single Recurrent Neoepitope in TCGA HER2+ BRCA Use a QR Scanner to download this Poster
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Filtering High-Quality Neoepitopes Across Cancers
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2000 UCEC (14)
THCA (10)
STAD (1)
READ (4)
PRAD (10)
LUSC (15)
LUAD (17)
KIRC (13)
HNSC (25)
COAD (3)
BRCA (28)
BLCA (3) 0
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Shared Neoepitopes Across Cancers
We would like to thank Kathryn Boorer, PhD, of NantHealth, LLC for writing assistance.
Acknowledgement
10%
90%
Normal Epitope
Neoepitope
Contact Corresponding Author: [email protected]
Neoepitopes (via WGS)
Coding Variants
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Non-Cancer Genes
Cancer Driving Genes
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Filtering High Quality Neoepitopes in TNBC
TCGA Barcode UCSC id HUGO Gene TPM Neoepitope
Protein Change Normal
Bound Allele
Bind Strength
TCGA-E2-A14X uc003ean.2 NAA50 229.85 PTDAHVLQK p.A145T PADAHVLQK A*11:01 146nM
TCGA-E2-A1LL uc001asj.3 FBXO2 187.36 LLLHVLAAL p.R57H LLLRVLAAL A*02:01 18nM
FDA Approved use of checkpoint inhibitors
Cancer Neoepitope Loads Across TCGA Dataset