867
Views
0
CrossRef citations to date
0
Altmetric
Review

Lost in the crowd: identifying targetable MHC class I neoepitopes for cancer immunotherapy

&
Pages 1065-1077 | Received 31 Jul 2018, Accepted 05 Nov 2018, Published online: 14 Nov 2018

References

  • Rock KL, Reits E, Neefjes J. Present yourself! By MHC class I and MHC class II molecules. Trends Immunol. 2016;37:724–737.
  • Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides, and coreceptors. Annu Rev Immunol. 2006;24:419–466.
  • Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957;18:769–778.
  • Wolfel T, Hauer M, Schneider J, et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science. 1995;269:1281–1284.
  • Zhou J, Dudley ME, Rosenberg SA, et al. Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother. 2005;28:53–62.
  • Lu Y-C, Yao X, Li YF, et al. Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression. J Immunol. 2013;190:6034–6042.
  • Van Rooij N, van Buuren MM, Philips D, et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Ocol. 2013;31(32):e439-442.
  • McGranahan N, Furness AJ, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–1469.
  • Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014;515:577–581.
  • Yadav M, Jhunjhunwala S, Phung QT, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515:572–576.
  • Kalaora S, Barnea E, Merhavi-Shoham E, et al. Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens. Oncotarget. 2016;7:5110.
  • Bassani-Sternberg M, Bräunlein E, Klar R, et al. Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nat commun. 2016;7:13404.
  • Khodadoust MS, Olsson N, Wagar LE, et al. Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens. Nature. 2017;543:723–727.
  • La Gruta NL, Gras S, Daley SR, et al. Understanding the drivers of MHC restriction of T cell receptors. Nat Rev Immunol. 2018;18(7):467-478.
  • Duan F, Duitama J, Al Seesi S, et al. Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity. J Exp Med. 2014;211:2231–2248.
  • Degano M, Garcia KC, Apostolopoulos V, et al. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity. 2000;12(3):251–261.
  • Fritsch EF, Rajasagi M, Ott PA, et al. HLA-binding properties of tumor neoepitopes in humans. Cancer Immunol Res. 2014;2:522–529.
  • Seifert U, Liermann H, Racanelli V, et al. Hepatitis C virus mutation affects proteasomal epitope processing. J Clin Invest. 2004;114:250–259.
  • Milicic A, Price DA, Zimbwa P, et al. CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef. J Immunol. 2005;175:4618–4626.
  • Eisenlohr LC, Yewdell J, Bennink J. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J Exp Medicine. 1992;175:481–487.
  • Beekman NJ, van Veelen PA, van Hall T, et al. Abrogation of CTL epitope processing by single amino acid substitution flanking the C-terminal proteasome cleavage site. J Immunol. 2000;164:1898–1905.
  • Carreno BM, Magrini V, Becker-Hapak M, et al. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015;348:803–808.
  • Hundal J, Carreno BM, Petti AA, et al. pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens. Genome Med. 2016;8:11.
  • Bjerregaard A-M, Nielsen M, Hadrup SR, et al. MuPeXI: prediction of neo-epitopes from tumor sequencing data. Cancer Immunol Immunother. 2017;66(9):1123–1130.
  • Sharma A, Wilson-Sayres M. EpitopeHunter. GitHub respository. 2018. Available from: https://github.com/WilsonSayresLab/Neoepitope_Prediction
  • Chowell D, Krishna S, Becker PD, et al. TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes. Proc Natl Acad Sci USA. 2015;112:E1754-E1762.
  • Kim S, Kim HS, Kim E, et al. Neopepsee: accurate genome-level prediction of neoantigens by harnessing sequence and amino acid immunogenicity information. Ann Oncol. 2018;29:1030–1036.
  • Sahin U, Türeci Ö. Personalized vaccines for cancer immunotherapy. Science. 2018;359(6382):1355–1360.
  • Ott PA, Hu Z, Keskin DB, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547:217.
  • Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547:222.
  • Castle JC, Kreiter S, Diekmann J, et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012;72:1081–1091.
  • Zacharakis N, Chinnasamy H, Black M, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat med. 2018;24(6):724-730.
  • Yarchoan M, Johnson III BA, Lutz ER, et al. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17:209–222.
  • Bjerregaard A-M, Nielsen M, Jurtz V, et al. an analysis of natural T cell responses to predicted tumor neoepitopes. Front Immunol. 2017;8:1566.
  • Mommen GPM, Frese CK, Meiring HD, et al. Expanding the detectable HLA peptide repertoire using electron-transfer/higher-energy collision dissociation (EThcD). Proc Natl Acad Sci. 2014;111:4507–4512.
  • Chong C, Marino F, Pak H, et al. High-throughput and sensitive immunopeptidomics platform reveals profound interferon-mediated remodeling of the human leukocyte antigen (HLA) ligandome. Mol Cell Proteom. 2018;17(3):533–548.
  • Abelin JG, Keskin DB, Sarkizova S, et al. Mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction. Immunity. 2017;46:315–326.
  • Ritz D, Kinzi J, Neri D, et al. Data-independent acquisition of HLA class I peptidomes on the Q exactive mass spectrometer platform. Proteomics. 2017;17(19):1700177.
  • Di Marco M, Schuster H, Backert L, et al. Unveiling the peptide motifs of HLA-C and HLA-G from naturally presented peptides and generation of binding prediction matrices. J Immunol. 2017;199:2639–2651.
  • Hassan C, Kester MGD, de Ru AH, et al. The human leukocyte antigen-presented ligandome of B lymphocytes. Mol Cell Proteom. 2013;12:1829–1843.
  • Sykulev Y, Joo M, Vturina I, et al. Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response. Immunity. 1996;4:565–571.
  • Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Ann Rev Immunol. 2009;27:591–619.
  • Sijts EJAM, Kloetzel PM. The role of the proteasome in the generation of MHC class I ligands and immune responses. Cell Mol Life Sci. 2011;68:1491–1502.
  • Rock KL, Gramm C, Rothstein L, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994;78:761–771.
  • Toes R, Nussbaum A, Degermann S, et al. Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products. J Exp Med. 2001;194:1–12.
  • Deol P, Zaiss DMW, Monaco JJ, et al. Rates of processing determine the immunogenicity of immunoproteasome-generated epitopes. J Immunol. 2007;178:7557–7562.
  • Tripathi SC, Peters HL, Taguchi A, et al. Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proc Natl Acad Sci. 2016;113:1555–1564.
  • Sijts AJ, Ruppert T, Rehermann B, et al. Efficient generation of a hepatitis B virus cytotoxic T lymphocyte epitope requires the structural features of immunoproteasomes. J Exp Med. 2000;191:503–514.
  • Schultz ES, Chapiro J, Lurquin C, et al. The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome. J Exp Med. 2002;195:391–399.
  • Anderson KS, Zeng W, Sasada T, et al. Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B cells and dendritic cells. Cancer Immunol Immunother. 2011;60:857–867.
  • Mishto M, Liepe J. Post-translational peptide splicing and T cell responses. Trends Immunol. 2017;38(12):904–915.
  • Ebstein F, Textoris-Taube K, Keller C, et al. Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes. Sci Rep. 2016;6:24032.
  • Liepe J, Marino F, Sidney J, et al. A large fraction of HLA class I ligands are proteasome-generated spliced peptides. Science. 2016;354:354–358.
  • Mylonas R, Beer I, Iseli C, et al. Estimating the contribution of proteasomal spliced peptides to the HLA-I ligandome. Mol Cell Proteom. 2018. DOI:10.1074/mcp.RA118.000877
  • Abele R, Tampé R. Moving the cellular peptidome by transporters. Front Cell Dev Bio. 2018;6:1–13.
  • Robinson J, Halliwell JA, Hayhurst JD, et al. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2014;43(D1):423–431.
  • Janeway CA Jr., Travers P, Walport M, et al. The major histocompatibility complex and its functions. New York (NY): Garland Science; 2001.
  • Trolle T, McMurtrey CP, Sidney J, et al. The length distribution of class I-restricted T cell epitopes is determined by both peptide supply and MHC allele-specific binding preference. J Immunol. 2016;196:1480–1487.
  • Matsumura M, Fremont DH, Peterson PA, et al. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science. 1992;257:927–934.
  • Burrows JM, Wynn KK, Tynan FE, et al. The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV. Eur J Immunol. 2007;37:946–953.
  • Calis JJA, Maybeno M, Greenbaum JA, et al. Properties of MHC class I presented peptides that enhance immunogenicity. PLoS Comput Biol. 2013;9:e1003266.
  • Rossjohn J, Gras S, Miles JJ, et al. T cell antigen receptor recognition of antigen-presenting molecules. Ann Rev Immunol. 2015;33:169–200.
  • Aptsiauri N, Ruiz-Cabello F, Garrido F. The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responses. Curr Opin Immunol. 2018;51:123–132.
  • Cai L, Michelakos T, Yamada T, et al. Defective HLA class I antigen processing machinery in cancer. Cancer Immunol Immunother. 2018;67:999–1009.
  • Del Campo AB, Kyte JA, Carretero J, et al. Immune escape of cancer cells with beta2-microglobulin loss over the course of metastatic melanoma. Int J Cancer. 2014;134:102–113.
  • Garrido F, Cabrera T, Aptsiauri N. “Hard” and “soft” lesions underlying the HLA class I alterations in cancer cells: implications for immunotherapy. Int J Cancer. 2010;127:249–256.
  • Carretero R, Wang E, Rodriguez AI, et al. Regression of melanoma metastases after immunotherapy is associated with activation of antigen presentation and interferon-mediated rejection genes. Int J Cancer. 2012;131:387–395.
  • Sade-Feldman M, Jiao YJ, Chen JH, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017;8(1):1136.
  • Rodig SJ, Gusenleitner D, Jackson DG, et al. MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma. Sci Transl Med. 2018;10(450):3342.
  • Bassani-Sternberg M, Pletscher-Frankild S, Jensen LJ, et al. Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation. Mol Cell Proteom. 2015;14:658–673.
  • Milner E, Barnea E, Beer I, et al. The turnover kinetics of major histocompatibility complex peptides of human cancer cells. Mol Cell Proteom. 2006;5:357–365.
  • Weinzierl AO, Lemmel C, Schoor O, et al. Distorted relation between mRNA copy number and corresponding major histocompatibility complex ligand density on the cell surface. Mol Cell Proteom. 2007;6:102–113.
  • Juncker AS, Larsen MV, Weinhold N, et al. Systematic characterisation of cellular localisation and expression profiles of proteins containing MHC ligands. PLoS One. 2009;4(10):e7448.
  • Rammensee H-G, Bachmann J, Emmerich NPN, et al. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999;50:213–219.
  • Kowalewski DJ, Schuster H, Backert L, et al. HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL). Proc Natl Acad Sci. 2015;112:166–175.
  • Klatt MG, Kowalewski DJ, Schuster H, et al. Carcinogenesis of renal cell carcinoma reflected in HLA ligands: A novel approach for synergistic peptide vaccination design. Oncoimmunology. 2016;5(8):e1204504.
  • Dutoit V, Herold-Mende C, Hilf N, et al. Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy. Brain. 2012;135:1042–1054.
  • Schuster H, Peper JK, Bӧsmüller H-C, et al. The immunopeptidomic landscape of ovarian carcinomas. Proc Natl Acad Sci. 2017;201707658.
  • Reits EA, Vos JC, Grommé M, et al. The major substrates for TAP invivo are derived from newly synthesized proteins. Nature. 2000;404:774–778.
  • Schubert U, Antón LC, Gibbs J, et al. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 2000;404:770–774.
  • Qian S-B, Princiotta MF, Bennink JR, et al. Characterization of rapidly degraded polypeptides in mammalian cells reveals a novel layer of nascent protein quality control. J Bio Chem. 2006;281:392–400.
  • Radivojac P, Vacic V, Haynes C, et al. Identification, analysis, and prediction of protein ubiquitination sites. Proteins Struct Funct Bioinform. 2010;78:365–380.
  • Yewdell JW, Antón LC, Bennink JR. Defective ribosomal products (DRiPs): a major source of antigenic peptides for MHC class I molecules? J Immunol. 1996;157:1823–1826.
  • Esquivel F, Yewdell J, Bennink J. RMA/S cells present endogenously synthesized cytosolic proteins to class I-restricted cytotoxic T lymphocytes. J Exp Med. 1992;175:163–168.
  • Antón LC, Yewdell JW. Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors. J Leukoc Bio. 2014;95:551–562.
  • Milner E, Gutter-Kapon L, Bassani-Strenberg M, et al. The effect of proteasome inhibition on the generation of the human leukocyte antigen (HLA) peptidome. Mol Cell Proteom. 2013;12:1853–1864.
  • Bourdetsky D, Schmelzer CEH, Admon A. The nature and extent of contributions by defective ribosome products to the HLA peptidome. Proc Natl Acad Sci. 2014;111:1591–1599.
  • Rock KL, Farfán-Arribas DJ, Colbert JD, et al. Re-examining class-I presentation and the DRiP hypothesis. Trends Immunol. 2014;35:144–152.
  • Pearson H, Daouda T, Granados DP, et al. MHC class I-associated peptides derive from selective regions of the human genome. J Clin Invest. 2016;126:4690–4701.
  • Schmidt M, Lill JR. MHC class I presented antigens from malignancies: A perspective on analytical characterization & immunogenicity. J Proteom. 2018. DOI: 10.1016/j.jprot.2018.04.021.
  • Gjerstorff MF, Andersen MH, Ditzel HJ. Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget. 2015;6(18):15772.
  • Mirandola L, Pedretti E, Figueroa JA, et al. Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy. Oncotarget. 2017;8:74378.
  • Robbins PF, Kassim SH, Tran TL, et al. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin Cancer Res. 2015;21:1019–1027.
  • Linette GP, Stadtmauer EA, Maus MV, et al. Cardiovascular toxicity and titin cross-reactivity of affinity enhanced T cells in myeloma and melanoma. Blood. 2013;122:863–871.
  • Morgan RA, Chinnasamy N, Abate-Daga DD, et al. Cancer regression and neurologic toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother. 2013;36:133.
  • Krishna S, Ulrich P, Wilson E, et al. Human papilloma virus specific immunogenicity and dysfunction of CD8+ T cells in head and neck cancer. Cancer Res. 2018;78:6159–6170.
  • Stevanović S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33:1543–1550.
  • Mesri EA, Feitelson MA, Munger K. Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe. 2014;15:266–282.
  • Laumont CM, Daouda T, Laverdure J-P, et al. Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames. Nat commun. 2016;7:10238.
  • Laumont CM, Perreault C. Exploiting non-canonical translation to identify new targets for T cell-based cancer immunotherapy. Cell Mol Life Sci. 2018;75(4):607-621.
  • Mertens F, Johansson B, Fioretos T, et al. The emerging complexity of gene fusions in cancer. Nat Rev Cancer. 2015;15:371–381.
  • Cai A, Keskin DB, DeLuca D, et al. Mutated BCR-ABL generates immunogenic t cell epitopes in CML patients. Clin Cancer Res. 2012;18:5761–5772.
  • Kalina JL, Neilson DS, Lin -Y-Y, et al. Mutational analysis of gene fusions predicts novel MHC class I-restricted T-cell epitopes and immune signatures in a subset of prostate cancer. Clin Cancer Res. 2017;23:7596–7607.
  • Raposo B, Merky P, Lundqvist C, et al. T cells specific for post-translational modifications escape intrathymic tolerance induction. Nat commun. 2018;9:353.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
  • Zarling AL, Polefrone JM, Evans AM, et al. Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy. Proc Natl Acad Sci. 2006;103:14889–14894.
  • Cobbold M, De La Peña H, Norris A, et al. MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. Sci transl med. 2013;5(203):203ra125.
  • Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015;15:540–555.
  • Marino F, Bern M, Mommen GP, et al. Extended O-GlcNAc on HLA class-I-bound peptides. J Am Chem Soc. 2015;137:10922–10925.
  • Pathangey LB, Lakshminarayanan V, Suman VJ, et al. Aberrant glycosylation of anchor-optimized MUC1 peptides can enhance antigen binding affinity and reverse tolerance to cytotoxic T lymphocytes. Biomolecules. 2016;6:31.
  • Lakshminarayanan V, Thompson P, Wolfert MA, et al. Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proc Natl Acad Sci. 2012;109(1):261–266.
  • Caron E, Kowalewski DJ, Koh CC, et al. Analysis of major histocompatibility complex (MHC) immunopeptidomes using mass spectrometry. Mol Cell Proteom. 2015;14:3105–3117.
  • Berlin C, Kowalewski D, Schuster H, et al. Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy. Leukemia. 2015;29:647–659.
  • Croft NP, Smith SA, Wong YC, et al. Kinetics of antigen expression and epitope presentation during virus infection. PLoS Pathog. 2013;9:e1003129.
  • Bassani-Sternberg M, Coukos G. Mass spectrometry-based antigen discovery for cancer immunotherapy. Curr Opin Immunol. 2016;41:9–17.
  • Lanoix J, Durette C, Courcelles M, et al. Comparison of the MHC I immunopeptidome repertoire of B-cell lymphoblasts using two isolation methods. Proteomics. 2018;18:1700251.
  • Hassan C, Kester MG, Oudgenoeg G, et al. Accurate quantitation of MHC-bound peptides by application of isotopically labeled peptide MHC complexes. J Proteom. 2014;109:240–244.
  • Gfeller D, Bassani-Sternberg M. Predicting antigen presentation-what could we learn from a million peptides? Front Immunol. 2018;9:1–17.
  • Bassani-Sternberg M, Chong C, Guillaume P, et al. Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity. PLoS Comput Bio. 2017;13:e1005725.
  • Nesvizhskii AI. A survey of computational methods and error rate estimation procedures for peptide and protein identification in shotgun proteomics. J Proteom. 2010;73:2092–2123.
  • Murphy JP, Konda P, Kowalewski DJ, et al. MHC-I ligand discovery using targeted database searches of mass spectrometry data: implications for T-cell immunotherapies. J Proteom Res. 2017;16:1806–1816.
  • Gillet LC, Navarro P, Tate S, et al. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteom. 2012;11:O111–O16717.
  • Rӧst HL, Rosenberger G, Navarro P, et al. OpenSWATH enables automated, targeted analysis of data-independent acquisition MS data. Nat Biotechnol. 2014;32:219–223.
  • Caron E, Espona L, Kowalewski DJ, et al. An open-source computational and data resource to analyze digital maps of immunopeptidomes. Elife. 2015;4:e07661.
  • Peckner R, Myers SA, Jacome ASV, et al. Specter: linear deconvolution for targeted analysis of data-independent acquisition mass spectrometry proteomics. Nat Methods. 2018;15:371–378.
  • Tsou -C-C, Avtonomov D, Larsen B, et al. DIA-Umpire: comprehensive computational framework for data-independent acquisition proteomics. Nat Methods. 2015;12:258–264.
  • Ting YS, Egertson JD, Bollinger JG, et al. PECAN: library-free peptide detection for data-independent acquisition tandem mass spectrometry data. Nat Methods. 2017;14:903–908.
  • Sanchez-Trincado JL, Gomez-Perosanz M, Reche PA. Fundamentals and methods for T-and B-cell epitope prediction. J Immunol Res. 2017. DOI:10.1155/2017/2680160
  • Mishra S, Sinha S. Prediction and molecular modeling of T-cell epitopes derived from placental alkaline phosphatase for use in cancer immunotherapy. J Biomol Struct Dyn. 2006;24:109–121.
  • Bentzen AK, Marquard AM, Lyngaa R, et al. Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. Nat biotechnol. 2016;34:1037–1045.
  • Verdegaal EM, van der Burg SH. The potential and challenges of exploiting the vast but dynamic neoepitope landscape for immunotherapy. Front Immunol. 2017;8:1113.
  • Corbière V, Chapiro J, Stroobant V, et al. Antigen spreading contributes to MAGE vaccination-induced regression of melanoma metastases. Cancer Res. 2011;71:1253–1262.
  • Karanikas V, Colau D, Baurain J-F, et al. High frequency of cytolytic T lymphocytes directed against a tumor-specific mutated antigen detectable with HLA tetramers in the blood of a lung carcinoma patient with long survival. Cancer Res. 2001;61:3718–3724.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.