{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:59:33Z","timestamp":1770821973513,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Akamis Bio Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1007\/s10637-023-01345-8","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T13:02:53Z","timestamp":1678453373000},"page":"317-323","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies"],"prefix":"10.1007","volume":"41","author":[{"given":"Danny N.","family":"Khalil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Prieto Gonz\u00e1lez-Albo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Lillie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Stacey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lola","family":"Parfitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald A.","family":"Soff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"issue":"1","key":"1345_CR1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40425-019-0510-7","volume":"7","author":"JP Machiels","year":"2019","unstructured":"Machiels JP, Salazar R, Rottey S, Duran I, Dirix L, Geboes K et al (2019) A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE). J Immunother Cancer 7(1):20","journal-title":"J Immunother Cancer"},{"issue":"12","key":"1345_CR2","doi-asserted-by":"publisher","first-page":"e003645","DOI":"10.1136\/jitc-2021-003645","volume":"9","author":"V Moreno","year":"2021","unstructured":"Moreno V, Barretina-Ginesta M-P, Garc\u00eda-Donas J, Jayson GC, Roxburgh P, V\u00e1zquez RM et al (2021) Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: a phase 1 clinical trial. J Immunother Cancer 9(12):e003645","journal-title":"J Immunother Cancer"},{"issue":"1","key":"1345_CR3","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s40425-017-0277-7","volume":"5","author":"R Garcia-Carbonero","year":"2017","unstructured":"Garcia-Carbonero R, Salazar R, Duran I, Osman-Garcia I, Paz-Ares L, Bozada JM et al (2017) Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection. J Immunother Cancer 5(1):71","journal-title":"J Immunother Cancer"},{"issue":"21","key":"1345_CR4","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1056\/NEJMra1705454","volume":"378","author":"D Garcia","year":"2018","unstructured":"Garcia D, Erkan D (2018) Diagnosis and management of the Antiphospholipid Syndrome. N Engl J Med 378(21):2010\u20132021","journal-title":"N Engl J Med"},{"issue":"2","key":"1345_CR5","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","volume":"4","author":"S Miyakis","year":"2006","unstructured":"Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, CERVERA R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4(2):295\u2013306","journal-title":"J Thromb Haemost"},{"issue":"3","key":"1345_CR6","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/ijlh.12234","volume":"36","author":"KM Devreese","year":"2014","unstructured":"Devreese KM (2014) Antiphospholipid antibody testing and standardization. Int J Lab Hematol 36(3):352\u2013363","journal-title":"Int J Lab Hematol"},{"issue":"10","key":"1345_CR7","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1111\/jth.14261","volume":"16","author":"W Chayoua","year":"2018","unstructured":"Chayoua W, Kelchtermans H, Moore GW, Musia\u0142 J, Wahl D, de Laat B et al (2018) Identification of high thrombotic risk triple-positive antiphospholipid syndrome patients is dependent on anti-cardiolipin and anti-\u03b22glycoprotein I antibody detection assays. J Thromb Haemost 16(10):2016\u20132023","journal-title":"J Thromb Haemost"},{"issue":"1","key":"1345_CR8","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/jth.14633","volume":"18","author":"W Chayoua","year":"2020","unstructured":"Chayoua W, Kelchtermans H, Gris JC, Moore GW, Musia\u0142 J, Wahl D et al (2020) The (non-)sense of detecting anti-cardiolipin and anti-\u03b22glycoprotein I IgM antibodies in the antiphospholipid syndrome. J Thromb Haemost 18(1):169\u2013179","journal-title":"J Thromb Haemost"},{"issue":"2","key":"1345_CR9","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1111\/jth.15585","volume":"20","author":"A Vandevelde","year":"2022","unstructured":"Vandevelde A, Chayoua W, de Laat B, Gris J-C, Moore GW, Musia\u0142 J et al (2022) Semiquantitative interpretation of anticardiolipin and anti\u03b22glycoprotein I antibodies measured with various analytical platforms: communication from the ISTH SSC Subcommittee on Lupus Anticoagulant\/Antiphospholipid antibodies. J Thromb Haemost 20(2):508\u2013524","journal-title":"J Thromb Haemost"},{"issue":"5","key":"1345_CR10","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1136\/ard.62.5.388","volume":"62","author":"RA Asherson","year":"2003","unstructured":"Asherson RA, Cervera R (2003) Antiphospholipid antibodies and infections. Ann Rheum Dis 62(5):388\u2013393","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"1345_CR11","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1177\/0961203317731532","volume":"27","author":"N Abdel-Wahab","year":"2018","unstructured":"Abdel-Wahab N, Talathi S, Lopez-Olivo MA, Suarez-Almazor ME (2018) Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis. Lupus 27(4):572\u2013583","journal-title":"Lupus"},{"issue":"4","key":"1345_CR12","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/j.urology.2005.04.041","volume":"66","author":"BS Malaeb","year":"2005","unstructured":"Malaeb BS, Gardner TA, Margulis V, Yang L, Gillenwater JY, Chung LWK et al (2005) Elevated activated partial thromboplastin time during administration of first-generation adenoviral vectors for gene therapy for prostate cancer: identification of lupus anticoagulants. Urology 66(4):830\u2013834","journal-title":"Urology"},{"issue":"11","key":"1345_CR13","doi-asserted-by":"publisher","first-page":"e0166393","DOI":"10.1371\/journal.pone.0166393","volume":"11","author":"MC Crank","year":"2016","unstructured":"Crank MC, Wilson EM, Novik L, Enama ME, Hendel CS, Gu W et al (2016) Safety and Immunogenicity of a rAd35-EnvA prototype HIV-1 vaccine in combination with rAd5-EnvA in healthy adults (VRC 012). PLoS ONE 11(11):e0166393","journal-title":"PLoS ONE"},{"issue":"2","key":"1345_CR14","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.vaccine.2010.10.037","volume":"29","author":"JE Ledgerwood","year":"2010","unstructured":"Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G et al (2010) A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine 29(2):304\u2013313","journal-title":"Vaccine"},{"issue":"3","key":"1345_CR15","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/15376510802312464","volume":"5","author":"RL Sheets","year":"2008","unstructured":"Sheets RL, Stein J, Bailer RT, Koup RA, Andrews C, Nason M et al (2008) Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or Marburg are similar despite differing adenovirus serotype vector, manufacturer\u2019s construct, or gene inserts. J Immunotoxicol 5(3):315\u2013335","journal-title":"J Immunotoxicol"},{"issue":"14","key":"1345_CR16","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1182\/blood.2020007338","volume":"137","author":"FI Mulder","year":"2021","unstructured":"Mulder FI, Horv\u00e1th-Puh\u00f3 E, van Es N, van Laarhoven HWM, Pedersen L, Moik F et al (2021) Venous thromboembolism in cancer patients: a population-based cohort study. Blood 137(14):1959\u20131969","journal-title":"Blood"},{"issue":"10","key":"1345_CR17","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1182\/blood-2013-04-460121","volume":"122","author":"JF Timp","year":"2013","unstructured":"Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC (2013) Epidemiology of cancer-associated venous thrombosis. Blood 122(10):1712\u20131723","journal-title":"Blood"},{"key":"1345_CR18","doi-asserted-by":"crossref","unstructured":"Fakih M, Wang D, Harb W, Rosen L, Mahadevan D, Berlin J et al (2019) A phase I multicenter study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: an analysis of the metastatic colorectal cancer patients in the dose escalation phase. Ann Oncol 30(Suppl 5):V198\u2013V252","DOI":"10.1093\/annonc\/mdz246.089"},{"key":"1345_CR19","doi-asserted-by":"crossref","unstructured":"Krige D, Fakih M, Rosen L, Wang D, Harb W, Babiker H et al (2021) 342 Combining enadenotucirev and nivolumab increased tumour immune cell infiltration\/activation in patients with microsatellite-stable\/instability-low metastatic colorectal cancer in a phase 1 study. J Immunother Cancer 9(Suppl 2):A368\u2013A9","DOI":"10.1136\/jitc-2021-SITC2021.342"},{"key":"1345_CR20","doi-asserted-by":"publisher","first-page":"S853","DOI":"10.1016\/j.annonc.2021.08.1395","volume":"32","author":"A Naing","year":"2021","unstructured":"Naing A, Rosen L, Camidge RD, Khalil D, Davies J, Miles D et al (2021) 1011P FORTITUDE phase I study of NG-350A, a novel tumour-selective adenoviral vector expressing an anti-CD40 agonist antibody: Monotherapy dose escalation results. Ann Oncol 32:S853\u2013S4","journal-title":"Ann Oncol"},{"issue":"12Supplement","key":"1345_CR21","doi-asserted-by":"publisher","first-page":"CT213","DOI":"10.1158\/1538-7445.AM2022-CT213","volume":"82","author":"T Lillie","year":"2022","unstructured":"Lillie T, O\u2019Hara M, Ottensmeier C, Parkes E, Rosen L, Krige D et al (2022) Abstract CT213: a multicenter phase 1a\/b study of NG-350A, a tumor-selective anti-CD40-antibody expressing adenoviral vector, and pembrolizumab in patients with metastatic or advanced epithelial tumors (FORTIFY). Cancer Res 82(12Supplement):CT213\u2013CT","journal-title":"Cancer Res"},{"issue":"Suppl 2","key":"1345_CR22","first-page":"A793","volume":"10","author":"G Simon","year":"2022","unstructured":"Simon G, Subbiah V, Rosen L, Lenz H-J, Park H, Patel M et al (2022) 762 First-in-human phase 1a study of NG-641, a tumour-selective vector expressing a FAP-TAc bispecific antibody and immune enhancer module, in patients with metastatic\/advanced epithelial tumours (STAR). J Immunother Cancer 10(Suppl 2):A793\u2013A","journal-title":"J Immunother Cancer"},{"issue":"Suppl 2","key":"1345_CR23","doi-asserted-by":"publisher","first-page":"A467","DOI":"10.1136\/jitc-2021-SITC2021.437","volume":"9","author":"C Ottensmeier","year":"2021","unstructured":"Ottensmeier C, Evans M, King E, Karydis I, Lillie T, Krige D et al (2021) 437 A multicentre phase 1b study of NG-641, a novel transgene-armed and tumour-selective adenoviral vector, and pembrolizumab as neoadjuvant treatment for squamous cell carcinoma of the head and neck. J Immunother Cancer 9(Suppl 2):A467\u2013A","journal-title":"J Immunother Cancer"},{"issue":"12Supplement","key":"1345_CR24","doi-asserted-by":"publisher","first-page":"CT214","DOI":"10.1158\/1538-7445.AM2022-CT214","volume":"82","author":"T Lillie","year":"2022","unstructured":"Lillie T, Parkes E, Ottensmeier C, Krige D, Ravanfar B, Evilevitch V et al (2022) Abstract CT214: a multicenter phase 1a\/b study of NG-641, a tumor-selective transgene-expressing adenoviral vector, and nivolumab in patients with metastatic or advanced epithelial tumors (NEBULA). Cancer Res 82(12Supplement):CT214\u2013CT","journal-title":"Cancer Res"},{"issue":"1","key":"1345_CR25","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1177\/107602960401000112","volume":"10","author":"V Wiwanitkit","year":"2004","unstructured":"Wiwanitkit V (2004) Activated partial Thromboplastin Time abnormality in patients with Cholangiocarcinoma. Clin Appl Thromb Hemost 10(1):69\u201371","journal-title":"Clin Appl Thromb Hemost"},{"issue":"8","key":"1345_CR26","doi-asserted-by":"publisher","first-page":"e22571","DOI":"10.1002\/jcla.22571","volume":"32","author":"J Liu","year":"2018","unstructured":"Liu J, Li F, Shu K, Chen T, Wang X, Xie Y et al (2018) The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): interference of C-reactive protein. J Clin Lab Anal 32(8):e22571","journal-title":"J Clin Lab Anal"},{"issue":"2","key":"1345_CR27","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1160\/TH16-08-0615","volume":"117","author":"C Ay","year":"2017","unstructured":"Ay C, Pabinger I, Cohen AT (2017) Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb Haemost 117(2):219\u2013230","journal-title":"Thromb Haemost"},{"issue":"14","key":"1345_CR28","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1177\/0961203316640912","volume":"25","author":"N Abdel-Wahab","year":"2016","unstructured":"Abdel-Wahab N, Lopez-Olivo MA, Pinto-Patarroyo GP, Suarez-Almazor ME (2016) Systematic review of case reports of antiphospholipid syndrome following infection. Lupus 25(14):1520\u20131531","journal-title":"Lupus"},{"issue":"1","key":"1345_CR29","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1136\/ard.2005.045443","volume":"65","author":"Y Shoenfeld","year":"2006","unstructured":"Shoenfeld Y, Blank M, Cervera R, Font J, Raschi E, Meroni P-L (2006) Infectious origin of the antiphospholipid syndrome. Ann Rheum Dis 65(1):2\u20136","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"1345_CR30","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/S0889-857X(05)70219-2","volume":"27","author":"AE Gharavi","year":"2001","unstructured":"Gharavi AE, Pierangeli SS, Harris EN (2001) Origin of antiphospholipid antibodies. Rheum Dis Clin North Am 27(3):551\u2013563","journal-title":"Rheum Dis Clin North Am"},{"issue":"4","key":"1345_CR31","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/ncprheum0740","volume":"4","author":"B de Laat","year":"2008","unstructured":"de Laat B, Mertens K, de Groot PG (2008) Mechanisms of Disease: antiphospholipid antibodies\u2014from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol 4(4):192\u2013199","journal-title":"Nat Clin Pract Rheumatol"}],"updated-by":[{"DOI":"10.1007\/s10637-023-01369-0","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000}}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-023-01345-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-023-01345-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-023-01345-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T14:55:39Z","timestamp":1744210539000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-023-01345-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["1345"],"URL":"https:\/\/doi.org\/10.1007\/s10637-023-01345-8","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s10637-023-01369-0","asserted-by":"object"}]},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]},"assertion":[{"value":"16 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2023","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s10637-023-01369-0","URL":"https:\/\/doi.org\/10.1007\/s10637-023-01369-0","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Approval from the appropriate institutional review board and independent ethics committee was received for the protocol, amendments, and consent forms before initiating the study at each site.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval statement"}},{"order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}