{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T21:12:15Z","timestamp":1768079535955,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["E\u2010Rare3\/0002\/2015"],"award-info":[{"award-number":["E\u2010Rare3\/0002\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/135501\/2018"],"award-info":[{"award-number":["PD\/BD\/135501\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006111","name":"Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"publisher","award":["PD\/BD\/135501\/2018"],"award-info":[{"award-number":["PD\/BD\/135501\/2018"]}],"id":[{"id":"10.13039\/501100006111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent clinical trials have shown the potential of oncolytic adenoviruses as a cancer immunotherapy. A successful transition of oncolytic adenovirus to clinical applications requires efficient and good manufacturing practice compatible production and purification bioprocesses. Suspension cultures are preferable for virus production as they can reduce process costs and increase product quality and consistency. This work describes the adaptation of the A549 cell line to suspension culture in serum\u2010reduced medium validated by oncolytic adenovirus production in stirred tank bioreactor. Cell concentrations up to 3\u00a0\u00d7\u00a010<jats:sup>6<\/jats:sup> cells mL<jats:sup>\u22121<\/jats:sup> are obtained during the production process. At harvest 1.4\u00a0\u00d7\u00a010<jats:sup>10<\/jats:sup> infectious particles mL<jats:sup>\u22121<\/jats:sup> and 6.9 \u00b1 1.1\u00a0\u00d7\u00a010<jats:sup>10<\/jats:sup> viral genome mL<jats:sup>\u22121<\/jats:sup> are obtained corresponding to a viral genome: infectious particles ratio of 5.2 (\u00b1 1.9): 1 confirming the virus quality. Overall, the suspension characteristics of these A549 cells support an easily scalable, less time\u2010consuming, and more cost\u2010effective process for expanded success in the use of oncolytic viruses for cancer therapy.<\/jats:p>","DOI":"10.1002\/biot.201900411","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T01:23:43Z","timestamp":1579224223000},"source":"Crossref","is-referenced-by-count":13,"title":["Establishing Suspension Cell Cultures for Improved Manufacturing of Oncolytic Adenovirus"],"prefix":"10.1002","volume":"15","author":[{"given":"Ana Sofia","family":"Moreira","sequence":"first","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Av. da Rep\u00fablica Oeiras 2775\u2010412 Portugal"}]},{"given":"Ana Carina","family":"Silva","sequence":"additional","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"}]},{"given":"Marcos F. Q.","family":"Sousa","sequence":"additional","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Av. da Rep\u00fablica Oeiras 2775\u2010412 Portugal"}]},{"given":"\u00c5sa","family":"Hagner\u2010McWhirterc","sequence":"additional","affiliation":[{"name":"GE Healthcare Bio\u2010Sciences AB  Bj\u00f6rkgatan 30 751 84 Uppsala Sweden"}]},{"given":"Gustaf","family":"Ahl\u00e9nc","sequence":"additional","affiliation":[{"name":"GE Healthcare Bio\u2010Sciences AB  Bj\u00f6rkgatan 30 751 84 Uppsala Sweden"}]},{"given":"Mats","family":"Lundgren","sequence":"additional","affiliation":[{"name":"GE Healthcare Bio\u2010Sciences AB  Bj\u00f6rkgatan 30 751 84 Uppsala Sweden"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-6890","authenticated-orcid":false,"given":"Ana S.","family":"Coroadinha","sequence":"additional","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Av. da Rep\u00fablica Oeiras 2775\u2010412 Portugal"}]},{"given":"Paula M.","family":"Alves","sequence":"additional","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Av. da Rep\u00fablica Oeiras 2775\u2010412 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-6637","authenticated-orcid":false,"given":"Cristina","family":"Peixoto","sequence":"additional","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Av. da Rep\u00fablica Oeiras 2775\u2010412 Portugal"}]},{"given":"Manuel J. T.","family":"Carrondo","sequence":"additional","affiliation":[{"name":"iBET Instituto de Biologia Experimental e Tecnol\u00f3gica  Av. da Rep\u00fablica Oeiras 2780\u2010157 Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Av. da Rep\u00fablica Oeiras 2775\u2010412 Portugal"}]}],"member":"311","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.266"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4663"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2015.03.009"},{"key":"e_1_2_7_4_1","unstructured":"M.Celia Witten US Food and Drug Administration. FDA approves first\u2010of\u2010its\u2010kind product for the treatment of melanoma.2015."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.2064"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0158-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.30"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/v2081681"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652310793797694"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0734-9750(02)00030-7"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800276-6.00006-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2005.16.281"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012199504-1\/50007-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209045"},{"key":"e_1_2_7_15_1","first-page":"16","volume":"10","author":"Rowley J.","year":"2012","journal-title":"BioProcess Int."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2014.007"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.12665\/J17OA.Pincus"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4155\/pbp.14.16"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0040"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7312-5_6"},{"key":"e_1_2_7_21_1","first-page":"1","volume":"1","author":"Ep A.","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"e_1_2_7_22_1","unstructured":"GE \u2010 Healthcare life Sciences Optimization of Midstream Cell Lysis and Virus Filtration Steps in an Adenovirus Purification Process.2018."},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639045.2017.1278768"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/biol.1998.0134"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.18"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030621"},{"key":"e_1_2_7_27_1","first-page":"619","volume-title":"Animal Cell Technology: Developments Towards the 21st Century","author":"Scharfenberg K.","year":"2011"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-006-0008-2"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.03.016"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/537433a"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00186960"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0141-0229(94)00071-X"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-095-9_6"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.503"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp049644r"},{"key":"e_1_2_7_36_1","unstructured":"S. L.Simek FDA Perspectives on the Development and Use of the Adenoviral Reference Material. n.d."},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2014.08.013"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbiot.201900411","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.201900411","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biot.201900411","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.201900411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:28:58Z","timestamp":1759955338000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.201900411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,27]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/biot.201900411"],"URL":"https:\/\/doi.org\/10.1002\/biot.201900411","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,27]]},"article-number":"1900411"}}