{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:17:40Z","timestamp":1789769860387,"version":"4.0.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K08188"],"award-info":[{"award-number":["23K08188"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02393"],"award-info":[{"award-number":["24K02393"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23H00319"],"award-info":[{"award-number":["23H00319"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K18320"],"award-info":[{"award-number":["21K18320"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K27453"],"award-info":[{"award-number":["23K27453"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627002"],"award-info":[{"award-number":["JP223fa627002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Gastric cancer with peritoneal metastasis is associated with a poor prognosis. Current treatments, including the first-line therapy of combination chemotherapy with nivolumab for advanced recurrent gastric cancer, have shown limited efficacy against peritoneal dissemination. In this study, we evaluated neoantigen (neoAg)-mRNA lipid nanoparticle (LNP) as a potential agent in combination with anti-PD-1 therapy, focusing on its effects on neoAg-specific CD8<jats:sup>+<\/jats:sup> T cell responses and antitumor efficacy in a murine gastric cancer model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The mRNA, comprising a tandem minigene encoding three neoAgs identified from the murine gastric cancer YTN16 cell line, was synthesized by in vitro transcription and encapsulated within LNPs. NeoAg-specific CD8<jats:sup>+<\/jats:sup> T cells in the spleens and tumors were assessed by flow cytometry. The antitumor efficacy of the neoAg-mRNA-LNP vaccine, alone or in combination with anti-PD-1 antibody, was evaluated in both subcutaneous and peritoneal metastasis models of YTN16.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The neoAg-mRNA-LNP vaccine induced significantly higher frequencies of neoAg-specific CD8<jats:sup>+<\/jats:sup> T cells than the neoAg-dendritic cell vaccine, confirming its enhanced immunogenicity. NeoAg-mRNA-LNP vaccination led to robust tumor regression, achieving complete eradication in all treated mice, especially when combined with anti-PD-1 therapy. This effect was associated with an increase in neoAg-specific progenitor-exhausted and intermediate-exhausted CD8<jats:sup>+<\/jats:sup> T cells. In a peritoneal metastasis model, neoAg-mRNA-LNP monotherapy prevented peritoneal dissemination when administered prophylactically, and combination therapy with anti-PD-1 effectively suppressed tumor growth in a therapeutic setting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>NeoAg-mRNA-LNP vaccines elicit potent neoAg-specific CD8<jats:sup>+<\/jats:sup> T cell responses and show enhanced antitumor efficacy with anti-PD-1 therapy in gastric cancer with peritoneal metastasis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10120-025-01640-8","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:03:11Z","timestamp":1753920191000},"page":"825-836","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neoantigen mRNA vaccines induce progenitor-exhausted T cells that support anti-PD-1 therapy in gastric cancer with peritoneal metastasis"],"prefix":"10.1007","volume":"28","author":[{"given":"Koji","family":"Nagaoka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Anindita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kawamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiyo","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Akita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Itaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiko","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2631-3040","authenticated-orcid":false,"given":"Kazuhiro","family":"Kakimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"issue":"3","key":"1640_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u201363.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"1640_CR2","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1007\/s10120-017-0716-7","volume":"21","author":"H Katai","year":"2018","unstructured":"Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, et al. Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001\u20132007). Gastric Cancer. 2018;21(1):144\u201354.","journal-title":"Gastric Cancer"},{"issue":"3","key":"1640_CR3","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/ijc.28373","volume":"134","author":"I Thomassen","year":"2014","unstructured":"Thomassen I, van Gestel YR, van Ramshorst B, Luyer MD, Bosscha K, Nienhuijs SW, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014;134(3):622\u20138.","journal-title":"Int J Cancer"},{"key":"1640_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.864647","volume":"12","author":"A Prabhu","year":"2022","unstructured":"Prabhu A, Mishra D, Brandl A, Yonemura Y. Gastric cancer with peritoneal metastasis-a comprehensive review of current intraperitoneal treatment modalities. Front Oncol. 2022;12: 864647.","journal-title":"Front Oncol"},{"issue":"3","key":"1640_CR5","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/jso.23633","volume":"110","author":"U Rudloff","year":"2014","unstructured":"Rudloff U, Langan RC, Mullinax JE, Beane JD, Steinberg SM, Beresnev T, et al. Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial. J Surg Oncol. 2014;110(3):275\u201384.","journal-title":"J Surg Oncol"},{"issue":"6","key":"1640_CR6","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1245\/s10434-011-1631-5","volume":"18","author":"XJ Yang","year":"2011","unstructured":"Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575\u201381.","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"1640_CR7","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1200\/JCO.22.02867","volume":"42","author":"B Rau","year":"2024","unstructured":"Rau B, Lang H, Koenigsrainer A, Gockel I, Rau HG, Seeliger H, et al. Effect of hyperthermic intraperitoneal chemotherapy on cytoreductive surgery in gastric cancer with synchronous peritoneal metastases: the phase III GASTRIPEC-I trial. J Clin Oncol. 2024;42(2):146\u201356.","journal-title":"J Clin Oncol"},{"issue":"10294","key":"1640_CR8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","volume":"398","author":"YY Janjigian","year":"2021","unstructured":"Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27\u201340.","journal-title":"Lancet"},{"issue":"2","key":"1640_CR9","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/S1470-2045(21)00692-6","volume":"23","author":"YK Kang","year":"2022","unstructured":"Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(2):234\u201347.","journal-title":"Lancet Oncol"},{"issue":"1","key":"1640_CR10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ccell.2022.10.013","volume":"41","author":"L Lybaert","year":"2023","unstructured":"Lybaert L, Lefever S, Fant B, Smits E, De Geest B, Breckpot K, et al. Challenges in neoantigen-directed therapeutics. Cancer Cell. 2023;41(1):15\u201340.","journal-title":"Cancer Cell"},{"issue":"5","key":"1640_CR11","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1111\/cas.13569","volume":"109","author":"M Yamamoto","year":"2018","unstructured":"Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T, et al. Established gastric cancer cell lines transplantable into C57BL\/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 2018;109(5):1480\u201392.","journal-title":"Cancer Sci"},{"key":"1640_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers14010106","volume":"14","author":"K Nagaoka","year":"2021","unstructured":"Nagaoka K, Sun C, Kobayashi Y, Kanaseki T, Tokita S, Komatsu T, et al. Identification of neoantigens in two murine gastric cancer cell lines leading to the neoantigen-based immunotherapy. Cancers (Basel). 2021;14:1.","journal-title":"Cancers (Basel)"},{"issue":"1","key":"1640_CR13","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1146\/annurev-immunol-090222-110914","volume":"42","author":"A Baessler","year":"2024","unstructured":"Baessler A, Vignali DAA. T Cell Exhaustion. Annu Rev Immunol. 2024;42(1):179\u2013206.","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"1640_CR14","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","volume":"20","author":"BC Miller","year":"2019","unstructured":"Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, et al. Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol. 2019;20(3):326\u201336.","journal-title":"Nat Immunol"},{"issue":"10","key":"1640_CR15","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1158\/2326-6066.CIR-21-0265","volume":"9","author":"CY Chen","year":"2021","unstructured":"Chen CY, Ueha S, Ishiwata Y, Shichino S, Yokochi Yang S, et al. Combining an Alarmin HMGN1 peptide with PD-L1 blockade results in robust antitumor effects with a concomitant increase of stem-like\/progenitor exhausted CD8(+) T cells. Cancer Immunol Res. 2021;9(10):1214\u201328.","journal-title":"Cancer Immunol Res"},{"issue":"19","key":"1640_CR16","doi-asserted-by":"publisher","first-page":"18758","DOI":"10.1021\/acsnano.3c02251","volume":"17","author":"R Oyama","year":"2023","unstructured":"Oyama R, Ishigame H, Tanaka H, Tateshita N, Itazawa M, Imai R, et al. An ionizable lipid material with a vitamin E scaffold as an mRNA vaccine platform for efficient cytotoxic T cell responses. ACS Nano. 2023;17(19):18758\u201374.","journal-title":"ACS Nano"},{"issue":"4","key":"1640_CR17","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1084\/jem.20030448","volume":"98","author":"A Mart\u00edN-Fontecha","year":"2003","unstructured":"Mart\u00edN-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, et al. Regulation of dendritic cell migration to the draining lymph node. J Exp Med. 2003;98(4):615\u201321.","journal-title":"J Exp Med"},{"issue":"2","key":"1640_CR18","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/sj.gt.3302358","volume":"12","author":"N Okada","year":"2005","unstructured":"Okada N, Mori N, Koretomo R, Okada Y, Nakayama T, Yoshie O, et al. Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction. Gene Ther. 2005;12(2):129\u201339.","journal-title":"Gene Ther"},{"issue":"10111","key":"1640_CR19","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/S0140-6736(17)31827-5","volume":"390","author":"YK Kang","year":"2017","unstructured":"Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):2461\u201371.","journal-title":"Lancet"},{"issue":"1","key":"1640_CR20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s10120-021-01230-4","volume":"25","author":"YK Kang","year":"2022","unstructured":"Kang YK, Morita S, Satoh T, Ryu MH, Chao Y, Kato K, et al. Exploration of predictors of benefit from nivolumab monotherapy for patients with pretreated advanced gastric and gastroesophageal junction cancer: post hoc subanalysis from the ATTRACTION-2 study. Gastric Cancer. 2022;25(1):207\u201317.","journal-title":"Gastric Cancer"},{"issue":"1","key":"1640_CR21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1136\/gutjnl-2018-318070","volume":"69","author":"R Wang","year":"2020","unstructured":"Wang R, Song S, Harada K, Ghazanfari Amlashi F, Badgwell B, Pizzi MP, et al. Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response. Gut. 2020;69(1):18\u201331.","journal-title":"Gut"},{"issue":"1","key":"1640_CR22","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1186\/s12885-020-07477-x","volume":"20","author":"D Fujimori","year":"2020","unstructured":"Fujimori D, Kinoshita J, Yamaguchi T, Nakamura Y, Gunjigake K, Ohama T, et al. Established fibrous peritoneal metastasis in an immunocompetent mouse model similar to clinical immune microenvironment of gastric cancer. BMC Cancer. 2020;20(1):1014.","journal-title":"BMC Cancer"},{"key":"1640_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.969468","volume":"13","author":"K Takahashi","year":"2022","unstructured":"Takahashi K, Kurashina K, Yamaguchi H, Kanamaru R, Ohzawa H, Miyato H, et al. Altered intraperitoneal immune microenvironment in patients with peritoneal metastases from gastric cancer. Front Immunol. 2022;13: 969468.","journal-title":"Front Immunol"},{"key":"1640_CR24","doi-asserted-by":"crossref","unstructured":"Du WY, Masuda H, Nagaoka K, Yasuda T, Kuge K, Seto Y, et al. Janus kinase inhibitor overcomes resistance to immune checkpoint inhibitor treatment in peritoneal dissemination of gastric cancer in C57BL\/6 J mice. Gastric Cancer. 2024.","DOI":"10.1007\/s10120-024-01514-5"},{"issue":"5","key":"1640_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e26971","volume":"10","author":"R Deyhimfar","year":"2024","unstructured":"Deyhimfar R, Izady M, Shoghi M, Kazazi MH, Ghazvini ZF, Nazari H, et al. The clinical impact of mRNA therapeutics in the treatment of cancers, infections, genetic disorders, and autoimmune diseases. Heliyon. 2024;10(5): e26971.","journal-title":"Heliyon"},{"issue":"7963","key":"1640_CR26","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41586-023-06063-y","volume":"618","author":"LA Rojas","year":"2023","unstructured":"Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023;618(7963):144\u201350.","journal-title":"Nature"},{"issue":"41","key":"1640_CR27","doi-asserted-by":"publisher","first-page":"eadn9961","DOI":"10.1126\/sciadv.adn9961","volume":"10","author":"T Fan","year":"2024","unstructured":"Fan T, Xu C, Wu J, Cai Y, Cao W, Shen H, et al. Lipopolyplex-formulated mRNA cancer vaccine elicits strong neoantigen-specific T cell responses and antitumor activity. Sci Adv. 2024;10(41):eadn9961.","journal-title":"Sci Adv"}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01640-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-025-01640-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01640-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T13:12:15Z","timestamp":1757250735000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-025-01640-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1640"],"URL":"https:\/\/doi.org\/10.1007\/s10120-025-01640-8","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"assertion":[{"value":"12 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"HT and HA are inventors of a patent on the LNP chemicals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All institutional and national guidelines for the care and use of laboratory animals were followed. The animal use proposal and experimental protocol were reviewed and approved by the Kindai University Animal Committee (ID: KAME-2024-006).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal rights"}}]}}