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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THCA (10)

STAD (1)

READ (4)

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LUSC (15)

LUAD (17)

KIRC (13)

HNSC (25)

COAD (3)

BRCA (28)

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We would like to thank Kathryn Boorer, PhD, of NantHealth, LLC for writing assistance.

Acknowledgement

10%

90%

Normal Epitope

Neoepitope

Contact Corresponding Author: Andy.Nguyen@nantomics.com

Neoepitopes (via WGS)

Coding Variants

94%

6%

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