Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2019

Open Access 01-12-2019 | Melanoma | Review

Tumor neoantigens: from basic research to clinical applications

Authors: Tao Jiang, Tao Shi, Henghui Zhang, Jie Hu, Yuanlin Song, Jia Wei, Shengxiang Ren, Caicun Zhou

Published in: Journal of Hematology & Oncology | Issue 1/2019

Login to get access

Abstract

Tumor neoantigen is the truly foreign protein and entirely absent from normal human organs/tissues. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs) in the context of major histocompatibility complexes (MHCs) molecules. Emerging evidence has suggested that neoantigens play a critical role in tumor-specific T cell-mediated antitumor immune response and successful cancer immunotherapies. From a theoretical perspective, neoantigen is an ideal immunotherapy target because they are distinguished from germline and could be recognized as non-self by the host immune system. Neoantigen-based therapeutic personalized vaccines and adoptive T cell transfer have shown promising preliminary results. Furthermore, recent studies suggested the significant role of neoantigen in immune escape, immunoediting, and sensitivity to immune checkpoint inhibitors. In this review, we systematically summarize the recent advances of understanding and identification of tumor-specific neoantigens and its role on current cancer immunotherapies. We also discuss the ongoing development of strategies based on neoantigens and its future clinical applications.
Literature
1.
2.
3.
Ward JP, Gubin MM, Schreiber RD. The role of neoantigens in naturally occurring and therapeutically induced immune responses to cancer. Adv Immunol. 2016;130:25–74.CrossRefPubMedPubMedCentral
4.
5.
6.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9.CrossRefPubMed
7.
Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20.CrossRefPubMed
8.
9.
10.
Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5:615–25.CrossRefPubMed
11.
12.
Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer. 2014;14:135–46.CrossRefPubMed
13.
Stone JD, Harris DT, Kranz DM. TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity. Curr Opin Immunol. 2015;33:16–22.CrossRefPubMedPubMedCentral
14.
Pan RY, Chung WH, Chu MT, Chen SJ, Chen HC, Zheng L, Hung SI. Recent development and clinical application of cancer vaccine: targeting neoantigens. J Immunol Res. 2018;2018:4325874.CrossRefPubMedPubMedCentral
15.
Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991:3–11.
16.
17.
18.
Gross L. Intradermal immunization of C3H mice against a sarcoma that originated in an animal of the same line. Cancer Res. 1943;3:326–33.
19.
Foley EJ. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953;13:835–7.PubMed
20.
De Plaen E, Lurquin C, Van Pel A, Mariame B, Szikora JP, Wolfel T, Sibille C, Chomez P, Boon T. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum- antigen P91A and identification of the tum- mutation. Proc Natl Acad Sci U S A. 1988;85:2274–8.CrossRefPubMedPubMedCentral
21.
Robbins PF, El-Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA. A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med. 1996;183:1185–92.CrossRefPubMed
22.
Brandle D, Brasseur F, Weynants P, Boon T. Van den Eynde B. A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma. J Exp Med. 1996;183:2501–8.CrossRefPubMed
23.
Huang J, El-Gamil M, Dudley ME, Li YF, Rosenberg SA, Robbins PF. T cells associated with tumor regression recognize frameshifted products of the CDKN2A tumor suppressor gene locus and a mutated HLA class I gene product. J Immunol. 2004;172:6057–64.CrossRefPubMed
24.
Lennerz V, Fatho M, Gentilini C, Frye RA, Lifke A, Ferel D, Wolfel C, Huber C, Wolfel T. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc Natl Acad Sci U S A. 2005;102:16013–8.CrossRefPubMedPubMedCentral
25.
Zhou J, Dudley ME, Rosenberg SA, Robbins PF. 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.CrossRefPubMedPubMedCentral
26.
Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, Arthur CD, White JM, Chen YS, Shea LK, Hundal J, Wendl MC, Demeter R, Wylie T, Allison JP, Smyth MJ, Old LJ, Mardis ER, Schreiber RD. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 2012;482:400–4.CrossRefPubMedPubMedCentral
27.
Castle JC, Kreiter S, Diekmann J, Lower M, van de Roemer N, de Graaf J, Selmi A, Diken M, Boegel S, Paret C, Koslowski M, Kuhn AN, Britten CM, Huber C, Tureci O, Sahin U. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012;72:1081–91.CrossRefPubMed
28.
Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med. 2013;19:747–52.CrossRefPubMedPubMedCentral
29.
Linnemann C, van Buuren MM, Bies L, Verdegaal EM, Schotte R, Calis JJ, Behjati S, Velds A, Hilkmann H, Atmioui DE, Visser M, Stratton MR, Haanen JB, Spits H, van der Burg SH, Schumacher TN. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nat Med. 2015;21:81–5.CrossRefPubMed
30.
Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA. T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med. 2016;375:2255–62.CrossRefPubMedPubMedCentral
31.
Verdegaal EM, de Miranda NF, Visser M, Harryvan T, van Buuren MM, Andersen RS, Hadrup SR, van der Minne CE, Schotte R, Spits H, Haanen JB, Kapiteijn EH, Schumacher TN, van der Burg SH. Neoantigen landscape dynamics during human melanoma-T cell interactions. Nature. 2016;536:91–5.CrossRefPubMed
32.
Stevanovic S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B, Robins HS, Robbins PF, Klebanoff CA, Rosenberg SA, Hinrichs CS. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017;356:200–5.CrossRefPubMedPubMedCentral
33.
Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–8.CrossRefPubMedPubMedCentral
34.
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1–10.CrossRefPubMed
35.
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321–30.CrossRefPubMed
36.
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–99.CrossRefPubMedPubMedCentral
37.
Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, Sucker A, Hillen U, Foppen MHG, Goldinger SM, Utikal J, Hassel JC, Weide B, Kaehler KC, Loquai C, Mohr P, Gutzmer R, Dummer R, Gabriel S, Wu CJ, Schadendorf D, Garraway LA. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350:207–11.CrossRefPubMedPubMedCentral
38.
39.
McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, Watkins TB, Shafi S, Murugaesu N, Mitter R, Akarca AU, Linares J, Marafioti T, Henry JY, Van Allen EM, Miao D, Schilling B, Schadendorf D, Garraway LA, Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD, Shukla SA, Wu CJ, Peggs KS, Chan TA, Hadrup SR, Quezada SA, Swanton C. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351:1463–9.CrossRefPubMedPubMedCentral
40.
Duan F, Duitama J, Al Seesi S, Ayres CM, Corcelli SA, Pawashe AP, Blanchard T, McMahon D, Sidney J, Sette A, Baker BM, Mandoiu II, Srivastava PK. Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity. J Exp Med. 2014;211:2231–48.CrossRefPubMedPubMedCentral
41.
42.
Milicic A, Price DA, Zimbwa P, Booth BL, Brown HL, Easterbrook PJ, Olsen K, Robinson N, Gileadi U, Sewell AK, Cerundolo V, Phillips RE. CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef. J Immunol. 2005;175:4618–26.CrossRefPubMed
43.
Eisenlohr LC, Yewdell JW, Bennink JR. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J Exp Med. 1992;175:481–7.CrossRefPubMed
44.
45.
Pritchard AL, Burel JG, Neller MA, Hayward NK, Lopez JA, Fatho M, Lennerz V, Wolfel T, Schmidt CW. Exome sequencing to predict neoantigens in melanoma. Cancer Immunol Res. 2015;3:992–8.CrossRefPubMed
46.
Gubin MM, Artyomov MN, Mardis ER, Schreiber RD. Tumor neoantigens: building a framework for personalized cancer immunotherapy. J Clin Invest. 2015;125:3413–21.CrossRefPubMedPubMedCentral
47.
Jurtz V, Paul S, Andreatta M, Marcatili P, Peters B, Nielsen M. NetMHCpan-4.0: Improved peptide-MHC Class I interaction predictions integrating eluted ligand and peptide binding affinity data. J Immunol. 2017;199:3360–8.CrossRefPubMed
48.
Jensen KK, Andreatta M, Marcatili P, Buus S, Greenbaum JA, Yan Z, Sette A, Peters B, Nielsen M. Improved methods for predicting peptide binding affinity to MHC class II molecules. Immunology. 2018;154:394–406.CrossRefPubMedPubMedCentral
49.
O'Donnell TJ, Rubinsteyn A, Bonsack M, Riemer AB, Laserson U, Hammerbacher J. MHCflurry: open-source Class I MHC binding affinity prediction. Cell Syst. 2018;7:129–132 e124.CrossRefPubMed
50.
51.
Alvaro-Benito M, Morrison E, Abualrous ET, Kuropka B, Freund C. Quantification of HLA-DM-dependent major histocompatibility complex of Class II immunopeptidomes by the peptide landscape antigenic epitope alignment utility. Front Immunol. 2018;9:872.CrossRefPubMedPubMedCentral
52.
53.
Bjerregaard AM, Nielsen M, Jurtz V, Barra CM, Hadrup SR, Szallasi Z, Eklund AC. An analysis of natural T cell responses to predicted tumor neoepitopes. Front Immunol. 2017;8:1566.CrossRefPubMedPubMedCentral
54.
55.
Vita R, Overton JA, Greenbaum JA, Ponomarenko J, Clark JD, Cantrell JR, Wheeler DK, Gabbard JL, Hix D, Sette A, Peters B. The immune epitope database (IEDB) 3.0. Nucleic Acids Res. 2015;43:D405–12.CrossRefPubMed
56.
Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, Franci C, Cheung TK, Fritsche J, Weinschenk T, Modrusan Z, Mellman I, Lill JR, Delamarre L. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515:572–6.CrossRefPubMed
57.
58.
Abelin JG, Keskin DB, Sarkizova S, Hartigan CR, Zhang W, Sidney J, Stevens J, Lane W, Zhang GL, Eisenhaure TM, Clauser KR, Hacohen N, Rooney MS, Carr SA, Wu CJ. Mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction. Immunity. 2017;46:315–26.CrossRefPubMedPubMedCentral
59.
Bulik-Sullivan B, Busby J, Palmer CD, Davis MJ, Murphy T, Clark A, Busby M, Duke F, Yang A, Young L, Ojo NC, Caldwell K, Abhyankar J, Boucher T, Hart MG, Makarov V, Montpreville VT, Mercier O, Chan TA, Scagliotti G, Bironzo P, Novello S, Karachaliou N, Rosell R, Anderson I, Gabrail N, Hrom J, Limvarapuss C, Choquette K, Spira A, Rousseau R, Voong C, Rizvi NA, Fadel E, Frattini M, Jooss K, Skoberne M, Francis J, Yelensky R. Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification. Nat Biotechnol. 2018. https://​doi.​org/​10.​1038/​nbt.​4313.CrossRef
60.
Bjerregaard AM, Nielsen M, Hadrup SR, Szallasi Z, Eklund AC. MuPeXI: prediction of neo-epitopes from tumor sequencing data. Cancer Immunol Immunother. 2017;66:1123–30.CrossRefPubMed
61.
Chowell D, Krishna S, Becker PD, Cocita C, Shu J, Tan X, Greenberg PD, Klavinskis LS, Blattman JN, Anderson KS. TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes. Proc Natl Acad Sci U S A. 2015;112:E1754–62.CrossRefPubMedPubMedCentral
62.
Wilson EA, Anderson KS. Lost in the crowd: identifying targetable MHC class I neoepitopes for cancer immunotherapy. Expert Rev Proteomics. 2018;15:1065–77.CrossRefPubMed
63.
Kim S, Kim HS, Kim E, Lee MG, Shin EC, Paik S, Kim S. Neopepsee: accurate genome-level prediction of neoantigens by harnessing sequence and amino acid immunogenicity information. Ann Oncol. 2018;29:1030–6.PubMed
64.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.CrossRefPubMed
65.
DuPage M, Cheung AF, Mazumdar C, Winslow MM, Bronson R, Schmidt LM, Crowley D, Chen J, Jacks T. Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression. Cancer Cell. 2011;19:72–85.CrossRefPubMedPubMedCentral
66.
67.
von Boehmer L, Mattle M, Bode P, Landshammer A, Schafer C, Nuber N, Ritter G, Old L, Moch H, Schafer N, Jager E, Knuth A, van den Broek M. NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma. Cancer Immun. 2013;13:12.
68.
Mittal D, Gubin MM, Schreiber RD, Smyth MJ. New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape. Curr Opin Immunol. 2014;27:16–25.CrossRefPubMedPubMedCentral
69.
70.
71.
van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B, van Dijk LJ, Behjati S, Hilkmann H, El Atmioui D, Nieuwland M, Stratton MR, Kerkhoven RM, Kesmir C, Haanen JB, Kvistborg P, Schumacher TN. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol. 2013;31:e439–42.CrossRefPubMed
72.
Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.CrossRefPubMedPubMedCentral
73.
Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, Zhang T, Adleff V, Phallen J, Wali N, Hruban C, Guthrie VB, Rodgers K, Naidoo J, Kang H, Sharfman W, Georgiades C, Verde F, Illei P, Li QK, Gabrielson E, Brock MV, Zahnow CA, Baylin SB, Scharpf RB, Brahmer JR, Karchin R, Pardoll DM, Velculescu VE. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017;7:264–76.CrossRefPubMed
74.
Angelova M, Mlecnik B, Vasaturo A, Bindea G, Fredriksen T, Lafontaine L, Buttard B, Morgand E, Bruni D, Jouret-Mourin A, Hubert C, Kartheuser A, Humblet Y, Ceccarelli M, Syed N, Marincola FM, Bedognetti D, Van den Eynde M, Galon J. Evolution of metastases in space and time under immune selection. Cell. 2018;175:751–765 e716.CrossRefPubMed
75.
Davidson G, Coassolo S, Kieny A, Ennen M, Pencreach E, Malouf GG, Lipsker D, Davidson I. Dynamic evolution of clonal composition and neoantigen landscape in recurrent metastatic melanoma with a rare combination of driver mutations. J Invest Dermatol. 2019;139:1769.CrossRefPubMed
76.
Nejo T, Matsushita H, Karasaki T, Nomura M, Saito K, Tanaka S, Takayanagi S, Hana T, Takahashi S, Kitagawa Y, Koike T, Kobayashi Y, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Narita Y, Nagane M, Ueki K, Nishikawa R, Aburatani H, Mukasa A, Saito N, Kakimi K. Reduced neoantigen expression revealed by longitudinal multiomics as a possible immune evasion mechanism in glioma. Cancer Immunol Res. 2019;7:1148–61.CrossRefPubMed
77.
Rosenthal R, Cadieux EL, Salgado R, Bakir MA, Moore DA, Hiley CT, Lund T, Tanic M, Reading JL, Joshi K, Henry JY, Ghorani E, Wilson GA, Birkbak NJ, Jamal-Hanjani M, Veeriah S, Szallasi Z, Loi S, Hellmann MD, Feber A, Chain B, Herrero J, Quezada SA, Demeulemeester J, Van Loo P, Beck S, McGranahan N, Swanton C, consortium TR. Neoantigen-directed immune escape in lung cancer evolution. Nature. 2019;567:479–85.CrossRefPubMedPubMedCentral
78.
Zhang J, Caruso FP, Sa JK, Justesen S, Nam DH, Sims P, Ceccarelli M, Lasorella A, Iavarone A. The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival. Commun Biol. 2019;2:135.CrossRefPubMedPubMedCentral
79.
Balachandran VP, Luksza M, Zhao JN, Makarov V, Moral JA, Remark R, Herbst B, Askan G, Bhanot U, Senbabaoglu Y, Wells DK, Cary CIO, Grbovic-Huezo O, Attiyeh M, Medina B, Zhang J, Loo J, Saglimbeni J, Abu-Akeel M, Zappasodi R, Riaz N, Smoragiewicz M, Kelley ZL, Basturk O, Australian Pancreatic Cancer Genome I, Garvan Institute of Medical R, Prince of Wales H, Royal North Shore H, University of G, St Vincent's H, Institute QBMR, University of Melbourne CfCR, University of Queensland IfMB, Bankstown H, Liverpool H, Royal Prince Alfred Hospital COBL, Westmead H, Fremantle H, St John of God H, Royal Adelaide H, Flinders Medical C, Envoi P, Princess Alexandria H, Austin H, Johns Hopkins Medical I, Cancer AR-NCfARo, Gonen M, Levine AJ, Allen PJ, Fearon DT, Merad M, Gnjatic S, Iacobuzio-Donahue CA, Wolchok JD, DeMatteo RP, Chan TA, Greenbaum BD, Merghoub T, Leach SD. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 2017; 551: 512-516.CrossRefPubMedPubMedCentral
80.
Dunn J, Rao S. Epigenetics and immunotherapy: the current state of play. Mol Immunol. 2017;87:227–39.CrossRefPubMed
81.
Garrido F, Ruiz-Cabello F, Aptsiauri N. Rejection versus escape: the tumor MHC dilemma. Cancer Immunol Immunother. 2017;66:259–71.CrossRefPubMed
82.
83.
84.
Melero I, Gaudernack G, Gerritsen W, Huber C, Parmiani G, Scholl S, Thatcher N, Wagstaff J, Zielinski C, Faulkner I, Mellstedt H. Therapeutic vaccines for cancer: an overview of clinical trials. Nat Rev Clin Oncol. 2014;11:509–24.CrossRefPubMed
85.
Yarchoan M, Johnson BA 3rd, Lutz ER, Laheru DA, Jaffee EM. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17:569.CrossRefPubMed
86.
Kreiter S, Vormehr M, van de Roemer N, Diken M, Lower M, Diekmann J, Boegel S, Schrors B, Vascotto F, Castle JC, Tadmor AD, Schoenberger SP, Huber C, Tureci O, Sahin U. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520:692–6.CrossRefPubMedPubMedCentral
87.
Aurisicchio L, Salvatori E, Lione L, Bandini S, Pallocca M, Maggio R, Fanciulli M, De Nicola F, Goeman F, Ciliberto G, Conforti A, Luberto L, Palombo F. Poly-specific neoantigen-targeted cancer vaccines delay patient derived tumor growth. J Exp Clin Cancer Res. 2019;38:78.CrossRefPubMedPubMedCentral
88.
Duperret EK, Perales-Puchalt A, Stoltz R, HH G, Mandloi N, Barlow J, Chaudhuri A, Sardesai NY, Weiner DB. A synthetic DNA, multi-neoantigen vaccine drives predominately MHC Class I CD8(+) T-cell responses, impacting tumor challenge. Cancer Immunol Res. 2019;7:174–82.CrossRefPubMedPubMedCentral
89.
Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat Mater. 2017;16:489–96.CrossRefPubMed
90.
Forghanifard MM, Gholamin M, Moaven O, Farshchian M, Ghahraman M, Aledavood A, Abbaszadegan MR. Neoantigen in esophageal squamous cell carcinoma for dendritic cell-based cancer vaccine development. Med Oncol. 2014;31:191.CrossRefPubMed
91.
Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arthur CD, Krebber WJ, Mulder GE, Toebes M, Vesely MD, Lam SS, Korman AJ, Allison JP, Freeman GJ, Sharpe AH, Pearce EL, Schumacher TN, Aebersold R, Rammensee HG, Melief CJ, Mardis ER, Gillanders WE, Artyomov MN, Schreiber RD. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014;515:577–81.CrossRefPubMedPubMedCentral
92.
Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M, Keil M, Balss J, Rauschenbach K, Grabowska AK, Vogler I, Diekmann J, Trautwein N, Eichmuller SB, Okun J, Stevanovic S, Riemer AB, Sahin U, Friese MA, Beckhove P, von Deimling A, Wick W, Platten M. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014;512:324–7.CrossRefPubMed
93.
Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015;348:803–8.CrossRefPubMedPubMedCentral
94.
Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanovic S, Gouttefangeas C, Platten M, Tabatabai G, Dutoit V, van der Burg SH, Thor Straten P, Martinez-Ricarte F, Ponsati B, Okada H, Lassen U, Admon A, Ottensmeier CH, Ulges A, Kreiter S, von Deimling A, Skardelly M, Migliorini D, Kroep JR, Idorn M, Rodon J, Piro J, Poulsen HS, Shraibman B, McCann K, Mendrzyk R, Lower M, Stieglbauer M, Britten CM, Capper D, Welters MJP, Sahuquillo J, Kiesel K, Derhovanessian E, Rusch E, Bunse L, Song C, Heesch S, Wagner C, Kemmer-Bruck A, Ludwig J, Castle JC, Schoor O, Tadmor AD, Green E, Fritsche J, Meyer M, Pawlowski N, Dorner S, Hoffgaard F, Rossler B, Maurer D, Weinschenk T, Reinhardt C, Huber C, Rammensee HG, Singh-Jasuja H, Sahin U, Dietrich PY, Wick W. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019;565:240–5.CrossRefPubMed
95.
Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, Shukla SA, Hu Z, Li L, Le PM, Allesoe RL, Richman AR, Kowalczyk MS, Abdelrahman S, Geduldig JE, Charbonneau S, Pelton K, Iorgulescu JB, Elagina L, Zhang W, Olive O, McCluskey C, Olsen LR, Stevens J, Lane WJ, Salazar AM, Daley H, Wen PY, Chiocca EA, Harden M, Lennon NJ, Gabriel S, Getz G, Lander ES, Regev A, Ritz J, Neuberg D, Rodig SJ, Ligon KL, Suva ML, Wucherpfennig KW, Hacohen N, Fritsch EF, Livak KJ, Ott PA, Wu CJ, Reardon DA. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565:234–9.CrossRefPubMed
96.
Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547:217–21.CrossRefPubMedPubMedCentral
97.
Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Lower M, Bukur V, Tadmor AD, Luxemburger U, Schrors B, Omokoko T, Vormehr M, Albrecht C, Paruzynski A, Kuhn AN, Buck J, Heesch S, Schreeb KH, Muller F, Ortseifer I, Vogler I, Godehardt E, Attig S, Rae R, Breitkreuz A, Tolliver C, Suchan M, Martic G, Hohberger A, Sorn P, Diekmann J, Ciesla J, Waksmann O, Bruck AK, Witt M, Zillgen M, Rothermel A, Kasemann B, Langer D, Bolte S, Diken M, Kreiter S, Nemecek R, Gebhardt C, Grabbe S, Holler C, Utikal J, Huber C, Loquai C, Tureci O. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547:222–6.CrossRefPubMed
98.
Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, Meng M, Fritz D, Vascotto F, Hefesha H, Grunwitz C, Vormehr M, Husemann Y, Selmi A, Kuhn AN, Buck J, Derhovanessian E, Rae R, Attig S, Diekmann J, Jabulowsky RA, Heesch S, Hassel J, Langguth P, Grabbe S, Huber C, Tureci O, Sahin U. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 2016;534:396–401.CrossRefPubMed
99.
Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, Gartner JJ, Zheng Z, Li YF, Ray S, Wunderlich JR, Somerville RP, Rosenberg SA. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science. 2015;350:1387–90.CrossRefPubMedPubMedCentral
100.
Yang W, Lee KW, Srivastava RM, Kuo F, Krishna C, Chowell D, Makarov V, Hoen D, Dalin MG, Wexler L, Ghossein R, Katabi N, Nadeem Z, Cohen MA, Tian SK, Robine N, Arora K, Geiger H, Agius P, Bouvier N, Huberman K, Vanness K, Havel JJ, Sims JS, Samstein RM, Mandal R, Tepe J, Ganly I, Ho AL, Riaz N, Wong RJ, Shukla N, Chan TA, Morris LGT. Immunogenic neoantigens derived from gene fusions stimulate T cell responses. Nat Med. 2019;25:767–75.CrossRefPubMedPubMedCentral
101.
Ren L, Leisegang M, Deng B, Matsuda T, Kiyotani K, Kato T, Harada M, Park JH, Saloura V, Seiwert T, Vokes E, Agrawal N, Nakamura Y. Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma. Oncoimmunology. 2019;8:e1568813.CrossRefPubMedPubMedCentral
102.
Veatch JR, Jesernig BL, Kargl J, Fitzgibbon M, Lee SM, Baik C, Martins R, Houghton AM, Riddell SR. Endogenous CD4(+) T cells recognize neoantigens in lung cancer patients, including recurrent oncogenic KRAS and ERBB2 (Her2) driver mutations. Cancer Immunol Res. 2019.
103.
Lo W, Parkhurst M, Robbins PF, Tran E, Lu YC, Jia L, Gartner JJ, Pasetto A, Deniger D, Malekzadeh P, Shelton TE, Prickett T, Ray S, Kivitz S, Paria BC, Kriley I, Schrump DS, Rosenberg SA. Immunologic recognition of a shared p53 mutated neoantigen in a patient with metastatic colorectal cancer. Cancer Immunol Res. 2019;7:534–43.CrossRefPubMedPubMedCentral
104.
Zhang X, Kim S, Hundal J, Herndon JM, Li S, Petti AA, Soysal SD, Li L, McLellan MD, Hoog J, Primeau T, Myers N, Vickery TL, Sturmoski M, Hagemann IS, Miller CA, Ellis MJ, Mardis ER, Hansen T, Fleming TP, Goedegebuure SP, Gillanders WE. Breast cancer neoantigens can induce CD8(+) T-cell responses and antitumor immunity. Cancer Immunol Res. 2017;5:516–23.CrossRefPubMedPubMedCentral
105.
Nelde A, Walz JS, Kowalewski DJ, Schuster H, Wolz OO, Peper JK, Cardona Gloria Y, Langerak AW, Muggen AF, Claus R, Bonzheim I, Fend F, Salih HR, Kanz L, Rammensee HG, Stevanovic S, Weber AN. HLA class I-restricted MYD88 L265P-derived peptides as specific targets for lymphoma immunotherapy. Oncoimmunology. 2017;6:e1219825.CrossRefPubMed
106.
Wang QJ, Yu Z, Griffith K, Hanada K, Restifo NP, Yang JC. Identification of T-cell receptors targeting KRAS-mutated human tumors. Cancer Immunol Res. 2016;4:204–14.CrossRefPubMed
107.
Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018;24:724–30.CrossRefPubMedPubMedCentral
108.
Cafri G, Yossef R, Pasetto A, Deniger DC, Lu YC, Parkhurst M, Gartner JJ, Jia L, Ray S, Ngo LT, Jafferji M, Sachs A, Prickett T, Robbins PF, Rosenberg SA. Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients. Nat Commun. 2019;10:449.CrossRefPubMedPubMedCentral
109.
Malekzadeh P, Pasetto A, Robbins PF, Parkhurst MR, Paria BC, Jia L, Gartner JJ, Hill V, Yu Z, Restifo NP, Sachs A, Tran E, Lo W, Somerville RP, Rosenberg SA, Deniger DC. Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers. J Clin Invest. 2019;129:1109–14.CrossRefPubMed
110.
Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344:641–5.CrossRefPubMedPubMedCentral
111.
Chen F, Zou Z, Du J, Su S, Shao J, Meng F, Yang J, Xu Q, Ding N, Yang Y, Liu Q, Wang Q, Sun Z, Zhou S, Du S, Wei J, Liu B. Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors. J Clin Invest. 2019;130.
112.
113.
Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18:168–82.CrossRefPubMed
114.
Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell. 2010;140:798–804.CrossRefPubMed
115.
Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res. 2015;21:687–92.CrossRefPubMed
116.
117.
118.
119.
Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, Mueller B, Quaratino S, Sabatos-Peyton C, Petruzzelli L, Engelman JA, Dranoff G. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017;17:286–301.CrossRefPubMed
120.
Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18:197–218.CrossRefPubMed
121.
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van ‘t Veer L, Vincent-Salomon A, Waddell N, Yates LR, Australian Pancreatic Cancer Genome I, Consortium IBC, Consortium IM-S, PedBrain I, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013;500:415–21.CrossRefPubMedPubMedCentral
122.
Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, Schrock A, Campbell B, Shlien A, Chmielecki J, Huang F, He Y, Sun J, Tabori U, Kennedy M, Lieber DS, Roels S, White J, Otto GA, Ross JS, Garraway L, Miller VA, Stephens PJ, Frampton GM. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9:34.CrossRefPubMedPubMedCentral
123.
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.CrossRefPubMedPubMedCentral
124.
Luksza M, Riaz N, Makarov V, Balachandran VP, Hellmann MD, Solovyov A, Rizvi NA, Merghoub T, Levine AJ, Chan TA, Wolchok JD, Greenbaum BD. A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy. Nature. 2017;551:517–20.CrossRefPubMedPubMedCentral
Metadata
Title
Tumor neoantigens: from basic research to clinical applications
Authors
Tao Jiang
Tao Shi
Henghui Zhang
Jie Hu
Yuanlin Song
Jia Wei
Shengxiang Ren
Caicun Zhou
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-019-0787-5

Other articles of this Issue 1/2019

Journal of Hematology & Oncology 1/2019 Go to the issue

Review

MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer

Research

Dual inhibition of IGF-IR and ALK as an effective strategy to eradicate NPM-ALK+ T-cell lymphoma

Review

K+-Cl− cotransporter 1 (KCC1): a housekeeping membrane protein that plays key supplemental roles in hematopoietic and cancer cells

Research

Burden of lymphoma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016

Review

Technologies for circulating tumor cell separation from whole blood

Review

Targeting CLL-1 for acute myeloid leukemia therapy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits