The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy

Author:

Martin Michael V.1ORCID,Aguilar-Rosas Salvador1ORCID,Franke Katka1ORCID,Pieterse Mark1ORCID,Langelaar Jamie van1ORCID,Schreurs Renée1ORCID,Bijlsma Maarten F.23ORCID,Besselink Marc G.34ORCID,Koster Jan2ORCID,Timens Wim5ORCID,Khasraw Mustafa6ORCID,Ashley David M.7ORCID,Keir Stephen T.6ORCID,Ottensmeier Christian H.8ORCID,King Emma V.9ORCID,Verheij Joanne10ORCID,Waasdorp Cynthia2ORCID,Valk Peter J.M.11ORCID,Engels Sem A.G.12ORCID,Oostenbach Ellen12ORCID,van Dinter Jip T.12ORCID,Hofman Damon A.12ORCID,Mok Juk Yee13ORCID,van Esch Wim J.E.13ORCID,Wilmink Hanneke314ORCID,Monkhorst Kim15ORCID,Verheul Henk M.W.16ORCID,Poel Dennis17ORCID,Hiltermann T. Jeroen N.18ORCID,Kempen Léon C.L.T. van519ORCID,Groen Harry J.M.18ORCID,Aerts Joachim G.J.V.20ORCID,Heesch Sebastiaan van12ORCID,Löwenberg Bob1ORCID,Plasterk Ronald1ORCID,Kloosterman Wigard P.1ORCID

Affiliation:

1. 1CureVac Netherlands B.V., Amsterdam, the Netherlands.

2. 2Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam, the Netherlands.

3. 3Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.

4. 4Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.

5. 5Department of Pathology and Medical Biology, University of Groningen, University, Medical Center Groningen, the Netherlands.

6. 6Duke University Medical Center, Duke University, Durham, North Carolina.

7. 7Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, North Carolina.

8. 8Liverpool Head and Neck Centre, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Clatterbridge Cancer Center NHS Foundation Trust, Liverpool, UK.

9. 9Department of Otorhinolaryngology, Head and Neck Surgery, Poole Hospital, Poole, UK.

10. 10Amsterdam UMC, location University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands.

11. 11Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.

12. 12The Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

13. 13Sanquin Reagents, Sanquin, Amsterdam, the Netherlands.

14. 14Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands.

15. 15Netherlands Cancer Institute, Amsterdam, the Netherlands.

16. 16Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

17. 17Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the, Netherlands.

18. 18Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, the Netherlands.

19. 19University of Antwerp, Antwerp University Hospital, Edegem, Belgium.

20. 20Erasmus Medical Center, Pulmonary Medicine, Rotterdam, the Netherlands.

Abstract

Abstract Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumors. We termed this collection of NOPs the tumor framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe a class of hidden NOPs that derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of noncoding regions of the genome downstream of a rearrangement breakpoint, i.e., where no gene annotation or evidence for transcription exists. The entire collection of NOPs represents a vast number of possible neoantigens particularly in tumors with many structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T cells specific for hidden NOPs in peripheral blood from a patient with lung cancer. This work highlights NOPs as a major source of possible neoantigens for personalized cancer immunotherapy and provides a rationale for analyzing the complete cancer genome and transcriptome as a basis for the detection of NOPs.

Funder

Eurostars European Commission

European Fund for Regional Development

Top Consortia for Knowledge and Innovation

Publisher

American Association for Cancer Research (AACR)

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. The neoantigens derived from transposable elements – A hidden treasure for cancer immunotherapy;Biochimica et Biophysica Acta (BBA) - Reviews on Cancer;2024-09

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3