{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:51:34Z","timestamp":1786125094729,"version":"build-2736575974"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Cell Int"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The neuronal pentraxin receptor (NPTXR) is mainly expressed in the cytoplasm of a subset of neuronal cells in the cerebral cortex. While NPTXR may be involved in mediating uptake of synaptic material during synapse remodeling or synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses during embryonic development,\n                      <jats:italic>NPTXR<\/jats:italic>\n                      expression has recently been shown to be elevated in tissues from patients with gastric cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      NPTXR protein expression was evaluated in human cancer and healthy tissue samples. We then generated antibody\u2013drug conjugates based on YB-800 (YB-800\n                      <jats:sub>ADCs<\/jats:sub>\n                      ), a fully humanized monoclonal antibody selectively targeting NPTXR. The cross-reactivity of YB-800 and YB-800\n                      <jats:sub>ADCs<\/jats:sub>\n                      were assessed, as well as their tumor inhibitory effects in experimental tumor models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NPTXR protein was highly and consistently expressed in human tissue samples from multiple cancer types but only minimally expressed, if at all, in healthy tissues. Treatment with YB-800\n                      <jats:sub>ADCs<\/jats:sub>\n                      inhibited tumor cell proliferation\/survival in engineered HEK293 cells overexpressing the human NPTXR. YB-800\n                      <jats:sub>ADCs<\/jats:sub>\n                      were also found to have pronounced anti-tumor effects in mice bearing NPTXR-expressing HEK293 tumors at well-tolerated doses. Initial anti-tumor findings were further confirmed using a naturally occurring NPTXR-expressing human bladder PDX model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      NPTXR is an oncofetal protein that is highly expressed in multiple human cancers but minimally expressed in healthy tissues. We have established NPTXR as a new tumor marker and have developed antibody\u2013drug conjugates using YB-800, a novel, first-in-class, humanized monoclonal antibody targeting the human NPTXR. Initial results demonstrate that YB-800\n                      <jats:sub>ADCs<\/jats:sub>\n                      have pronounced anti-tumor effects in vivo in NPTXR-expressing cancer cells. Continued evaluation of YB-800\n                      <jats:sub>ADCs<\/jats:sub>\n                      is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-026-04438-5","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:35:12Z","timestamp":1786120512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NPTXR as a novel therapeutic target: efficacy of antibody-drug conjugates in preclinical tumor models"],"prefix":"10.1186","volume":"26","author":[{"given":"Mykola","family":"Lyndin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Janicot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schiemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-2475","authenticated-orcid":false,"given":"Gunther","family":"Wennemuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"4438_CR1","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.neuron.2008.01.010","volume":"57","author":"RW Cho","year":"2008","unstructured":"Cho RW, Park JM, Wolff SB, Xu D, Hopf C, Kim JA, Reddy RC, Petralia RS, Perin MS, Linden DJ, Worley PF. mGluR1\/5-dependent long-term depression requires the regulated ectodomain cleavage of neuronal pentraxin NPR by TACE. Neuron. 2008;57:858\u201371.","journal-title":"Neuron"},{"key":"4438_CR2","doi-asserted-by":"publisher","first-page":"21488","DOI":"10.1074\/jbc.272.34.21488","volume":"272","author":"DC Dodds","year":"1997","unstructured":"Dodds DC, Omeis IA, Cushman SJ, Helms JA, Perin MS. Neuronal pentraxin receptor, a novel putative integral membrane pentraxin that interacts with neuronal pentraxin 1 and 2 and taipoxin-associated calcium-binding protein 49. J Biol Chem. 1997;272:21488\u201394.","journal-title":"J Biol Chem"},{"key":"4438_CR3","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00702-021-02411-2","volume":"129","author":"N Gomez de San Jose","year":"2022","unstructured":"Gomez de San Jose N, Massa F, Halbgebauer S, Oeckl P, Steinacker P, Otto M. Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration. J Neural Transm (Vienna). 2022;129:207\u201330.","journal-title":"J Neural Transm (Vienna)"},{"key":"4438_CR4","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1523\/JNEUROSCI.2768-16.2016","volume":"37","author":"SJ Lee","year":"2017","unstructured":"Lee SJ, Wei M, Zhang C, Maxeiner S, Pak C, Calado Botelho S, Trotter J, Sterky FH, Sudhof TC. Presynaptic Neuronal Pentraxin Receptor Organizes Excitatory and Inhibitory Synapses. J Neurosci. 2017;37:1062\u201380.","journal-title":"J Neurosci"},{"key":"4438_CR5","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/j.neuron.2015.02.020","volume":"85","author":"KA Pelkey","year":"2015","unstructured":"Pelkey KA, Barksdale E, Craig MT, Yuan X, Sukumaran M, Vargish GA, Mitchell RM, Wyeth MS, Petralia RS, Chittajallu R, et al. Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons. Neuron. 2015;85:1257\u201372.","journal-title":"Neuron"},{"key":"4438_CR6","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1146\/annurev-physiol-021317-121322","volume":"80","author":"M Yuzaki","year":"2018","unstructured":"Yuzaki M. Two Classes of Secreted Synaptic Organizers in the Central Nervous System. Annu Rev Physiol. 2018;80:243\u201362.","journal-title":"Annu Rev Physiol"},{"key":"4438_CR7","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12943-020-01251-0","volume":"19","author":"M Kanda","year":"2020","unstructured":"Kanda M, Shimizu D, Sawaki K, Nakamura S, Umeda S, Miwa T, Tanaka H, Tanaka C, Hayashi M, Iguchi Y, et al. Therapeutic monoclonal antibody targeting of neuronal pentraxin receptor to control metastasis in gastric cancer. Mol Cancer. 2020;19:131.","journal-title":"Mol Cancer"},{"key":"4438_CR8","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.3389\/fimmu.2020.01757","volume":"11","author":"Z Wang","year":"2020","unstructured":"Wang Z, Wang X, Zou H, Dai Z, Feng S, Zhang M, Xiao G, Liu Z, Cheng Q. The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression. Front Immunol. 2020;11:1757.","journal-title":"Front Immunol"},{"key":"4438_CR9","doi-asserted-by":"publisher","first-page":"e202500262","DOI":"10.1002\/cmdc.202500262","volume":"20","author":"Y Lei","year":"2025","unstructured":"Lei Y, Zheng M, Chen P, Seng Ng C, Peng Loh T, Liu H. Linker Design for the Antibody Drug Conjugates: A Comprehensive Review. ChemMedChem. 2025;20:e202500262.","journal-title":"ChemMedChem"},{"key":"4438_CR10","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s13045-023-01519-0","volume":"16","author":"A Lopez de Sa","year":"2023","unstructured":"Lopez de Sa A, Diaz-Tejeiro C, Poyatos-Racionero E, Nieto-Jimenez C, Paniagua-Herranz L, Sanvicente A, Calvo E, Perez-Segura P, Moreno V, Moris F, Ocana A. Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned. J Hematol Oncol. 2023;16:118.","journal-title":"J Hematol Oncol"},{"key":"4438_CR11","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1208\/s12248-016-9892-3","volume":"18","author":"KF Maass","year":"2016","unstructured":"Maass KF, Kulkarni C, Betts AM, Wittrup KD. Determination of Cellular Processing Rates for a Trastuzumab-Maytansinoid Antibody-Drug Conjugate (ADC) Highlights Key Parameters for ADC Design. AAPS J. 2016;18:635\u201346.","journal-title":"AAPS J"},{"key":"4438_CR12","doi-asserted-by":"crossref","unstructured":"Sheyi R, de la Torre BG, Albericio F. Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate. Pharmaceutics; 2022. p. 14.","DOI":"10.3390\/pharmaceutics14020396"},{"key":"4438_CR13","first-page":"362","volume":"5","author":"JY Fong","year":"2025","unstructured":"Fong JY, Phuna Z, Chong DY, Heryanto CM, Low YS, Oh KC, Lee YH, Ng AWR, In LLA, Teo MYM. Advancements in antibody-drug conjugates as cancer therapeutics. J Natl Cancer Cent. 2025;5:362\u201378.","journal-title":"J Natl Cancer Cent"},{"key":"4438_CR14","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13045-025-01704-3","volume":"18","author":"R Wang","year":"2025","unstructured":"Wang R, Hu B, Pan Z, Mo C, Zhao X, Liu G, Hou P, Cui Q, Xu Z, Wang W, et al. Antibody-Drug Conjugates (ADCs): current and future biopharmaceuticals. J Hematol Oncol. 2025;18:51.","journal-title":"J Hematol Oncol"},{"key":"4438_CR15","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/j.ccell.2022.09.016","volume":"40","author":"R Colombo","year":"2022","unstructured":"Colombo R, Rich JR. The therapeutic window of antibody drug conjugates: A dogma in need of revision. Cancer Cell. 2022;40:1255\u201363.","journal-title":"Cancer Cell"},{"key":"4438_CR16","first-page":"34","volume":"8","author":"M Zhou","year":"2025","unstructured":"Zhou M, Huang Z, Ma Z, Chen J, Lin S, Yang X, Gong Q, Braunstein Z, Wei Y, Rao X, Zhong J. The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy. Cancer Drug Resist. 2025;8:34.","journal-title":"Cancer Drug Resist"},{"key":"4438_CR17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12935-022-02679-8","volume":"22","author":"HE Marei","year":"2022","unstructured":"Marei HE, Cenciarelli C, Hasan A. Potential of antibody-drug conjugates (ADCs) for cancer therapy. Cancer Cell Int. 2022;22:255.","journal-title":"Cancer Cell Int"},{"key":"4438_CR18","doi-asserted-by":"publisher","first-page":"3287","DOI":"10.1158\/1078-0432.CCR-24-0426","volume":"30","author":"S Jain","year":"2024","unstructured":"Jain S, Griffith JI, Porath KA, Rathi S, Le J, Pasa TI, Decker PA, Gupta SK, Hu Z, Carlson BL, et al. Bystander Effects, Pharmacokinetics, and Linker-Payload Stability of EGFR-Targeting Antibody-Drug Conjugates Losatuxizumab Vedotin and Depatux-M in Glioblastoma Models. Clin Cancer Res. 2024;30:3287\u201397.","journal-title":"Clin Cancer Res"},{"key":"4438_CR19","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s12885-019-5336-7","volume":"19","author":"JH Byun","year":"2019","unstructured":"Byun JH, Jung IH. Modeling to capture bystander-killing effect by released payload in target positive tumor cells. BMC Cancer. 2019;19:194.","journal-title":"BMC Cancer"},{"key":"4438_CR20","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/ph14030247","volume":"9","author":"L Conilh","year":"2021","unstructured":"Conilh L, Fournet G, Fourmaux E, Murcia A, Matera EL, Joseph B, Dumontet C, Viricel W. Exatecan antibody drug conjugates based on a hydrophilic polysarcosine drug-linker platform. Pharmaceuticals. 2021;9:14:247.","journal-title":"Pharmaceuticals"}],"container-title":["Cancer Cell International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12935-026-04438-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04438-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04438-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:50:14Z","timestamp":1786121414000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12935-026-04438-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4438"],"URL":"https:\/\/doi.org\/10.1186\/s12935-026-04438-5","relation":{},"ISSN":["1475-2867"],"issn-type":[{"value":"1475-2867","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"11 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Use of human and mouse tissue for NPTXR expression testing and use of human cell lines did not require institutional ethics approval because this study used commercially available, de-identified human tissue microarrays purchased from TissueArray.Com LLC (US) and ProVitro AG and commercial cell lines from ATCC (US) or CrownBio Bioscience (China). All commercial suppliers provided statements of conformity with ethical requirements; no identifiable information was accessed. All in vivo procedures performed at Rincon Bio (USA) were conducted under IACUC-approved protocols and in accordance with institutional regulations for animal care and use. Studies adhered to the NIH Guide for the Care and Use of Laboratory Animals and relevant reporting guidelines. In vivo procedures conducted at EPO Berlin-Buch GmbH (Berlin, Germany) were conducted in accordance with the UKCCCR regulations for the Welfare of Animals and of the German Animal Protection Law and were approved by the local responsible authorities.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"ML declares no competing interests. PS is the founder of and a shareholder in Ymmunobio AG. MJ has received honoraria from Ymmunobio AG. GW is member of the advisory board of Ymmunobio.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"278"}}