{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T06:04:32Z","timestamp":1785045872379,"version":"3.55.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T00:00:00Z","timestamp":1475798400000},"content-version":"vor","delay-in-days":494,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2015,6]]},"DOI":"10.1038\/mt.2015.49","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T13:04:25Z","timestamp":1427288665000},"page":"1066-1076","source":"Crossref","is-referenced-by-count":71,"title":["Complement Inhibition Prevents Oncolytic Vaccinia Virus Neutralization in Immune Humans and Cynomolgus Macaques"],"prefix":"10.1016","volume":"23","author":[{"given":"Laura","family":"Evgin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio A","family":"Acuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiano","family":"Tanese de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Marguerie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal G","family":"Lemay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina S","family":"Ilkow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Scott","family":"Findlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Falls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley A","family":"Parato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hanwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lafrance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J","family":"Breitbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kirn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Atkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C","family":"Auer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M","family":"Thurman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory L","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Lambris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Andrea","family":"McCart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/mt.2015.49_bib1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nrc2545","article-title":"Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer","volume":"9","author":"Kirn","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"10.1038\/mt.2015.49_bib2","doi-asserted-by":"crossref","first-page":"e25595","DOI":"10.4161\/onci.25595","article-title":"Trial watch: anticancer radioimmunotherapy","volume":"2","author":"Vacchelli","year":"2013","journal-title":"Oncoimmunology"},{"key":"10.1038\/mt.2015.49_bib3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrmicro3140","article-title":"New viruses for cancer therapy: meeting clinical needs","volume":"12","author":"Miest","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"10.1038\/mt.2015.49_bib4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1470-2045(08)70107-4","article-title":"Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial","volume":"9","author":"Park","year":"2008","journal-title":"Lancet Oncol"},{"key":"10.1038\/mt.2015.49_bib5","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nm.3089","article-title":"Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer","volume":"19","author":"Heo","year":"2013","journal-title":"Nat Med"},{"key":"10.1038\/mt.2015.49_bib6","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1038\/mt.2011.132","article-title":"A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma","volume":"19","author":"Hwang","year":"2011","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2015.49_bib7","article-title":"OPTiM: a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB\/C and IV melanoma","volume":"31","author":"Ingemar Andtbacka","year":"2013","journal-title":"J Clin Oncol"},{"key":"10.1038\/mt.2015.49_bib8","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ymthe.2006.05.008","article-title":"Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF","volume":"14","author":"Kim","year":"2006","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2015.49_bib9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S1535-6108(03)00241-1","article-title":"VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents","volume":"4","author":"Stojdl","year":"2003","journal-title":"Cancer Cell"},{"key":"10.1038\/mt.2015.49_bib10","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat Immunol"},{"key":"10.1038\/mt.2015.49_bib11","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1348-0421.1968.tb00393.x","article-title":"Complement requirement of the neutralizing antibody appearing after immunization with smallpox vaccine","volume":"12","author":"Nishimura","year":"1968","journal-title":"Jpn J Microbiol"},{"key":"10.1038\/mt.2015.49_bib12","first-page":"529","article-title":"Two heat-labile factors in normal sera which neutralize variola virus","volume":"33","author":"McCarthy","year":"1952","journal-title":"Br J Exp Pathol"},{"key":"10.1038\/mt.2015.49_bib13","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1128\/IAI.8.4.582-589.1973","article-title":"Effect of heat-labile factors on the neutralization of vaccinia virus by human","volume":"8","author":"Takabayashi","year":"1973","journal-title":"Infect Immun"},{"key":"10.1038\/mt.2015.49_bib14","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1086\/518793","article-title":"Antibody responses to vaccinia membrane proteins after smallpox vaccination","volume":"196","author":"Lawrence","year":"2007","journal-title":"J Infect Dis"},{"key":"10.1038\/mt.2015.49_bib15","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nm917","article-title":"Duration of antiviral immunity after smallpox vaccination","volume":"9","author":"Hammarlund","year":"2003","journal-title":"Nat Med"},{"key":"10.1038\/mt.2015.49_bib16","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1128\/JVI.02244-07","article-title":"Redundancy and plasticity of neutralizing antibody responses are cornerstone attributes of the human immune response to the smallpox vaccine","volume":"82","author":"Benhnia","year":"2008","journal-title":"J Virol"},{"key":"10.1038\/mt.2015.49_bib17","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.4049\/jimmunol.171.10.4969","article-title":"Cutting edge: long-term B cell memory in humans after smallpox vaccination","volume":"171","author":"Crotty","year":"2003","journal-title":"J Immunol"},{"key":"10.1038\/mt.2015.49_bib18","first-page":"273","article-title":"Compstatin: a complement inhibitor on its way to clinical application","volume":"632","author":"Ricklin","year":"2008","journal-title":"Adv Exp Med Biol"},{"key":"10.1038\/mt.2015.49_bib19","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1182\/blood-2013-11-536573","article-title":"Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria","volume":"123","author":"Risitano","year":"2014","journal-title":"Blood"},{"key":"10.1038\/mt.2015.49_bib20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.imbio.2012.06.003","article-title":"New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties","volume":"218","author":"Qu","year":"2013","journal-title":"Immunobiology"},{"key":"10.1038\/mt.2015.49_bib21","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/jbm.a.32034","article-title":"Hirudin versus heparin for use in whole blood in vitro biocompatibility models","volume":"89","author":"Bexborn","year":"2009","journal-title":"J Biomed Mater Res A"},{"key":"10.1038\/mt.2015.49_bib22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature10358","article-title":"Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans","volume":"477","author":"Breitbach","year":"2011","journal-title":"Nature"},{"key":"10.1038\/mt.2015.49_bib23","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.4049\/jimmunol.160.11.5596","article-title":"Interaction of vaccinia virus complement control protein with human complement proteins: factor I-mediated degradation of C3b to iC3b1 inactivates the alternative complement pathway","volume":"160","author":"Sahu","year":"1998","journal-title":"J Immunol"},{"key":"10.1038\/mt.2015.49_bib24","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1073\/pnas.89.2.628","article-title":"Vaccinia virus complement-control protein prevents antibody-dependent complement-enhanced neutralization of infectivity and contributes to virulence","volume":"89","author":"Isaacs","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/mt.2015.49_bib25","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1126\/science.2237434","article-title":"Inhibition of the complement cascade by the major secretory protein of vaccinia virus","volume":"250","author":"Kotwal","year":"1990","journal-title":"Science"},{"key":"10.1038\/mt.2015.49_bib26","doi-asserted-by":"crossref","first-page":"7544","DOI":"10.1073\/pnas.95.13.7544","article-title":"Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope","volume":"95","author":"Vanderplasschen","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/mt.2015.49_bib27","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.1248943","article-title":"Complement is activated by IgG hexamers assembled at the cell surface","volume":"343","author":"Diebolder","year":"2014","journal-title":"Science"},{"key":"10.1038\/mt.2015.49_bib28","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1128\/JVI.74.10.4765-4775.2000","article-title":"Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant","volume":"74","author":"Ikeda","year":"2000","journal-title":"J Virol"},{"key":"10.1038\/mt.2015.49_bib29","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.mayocp.2014.04.003","article-title":"Remission of disseminated cancer after systemic oncolytic virotherapy","volume":"89","author":"Russell","year":"2014","journal-title":"Mayo Clin Proc"},{"key":"10.1038\/mt.2015.49_bib30","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/gt.2008.21","article-title":"Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial","volume":"15","author":"White","year":"2008","journal-title":"Gene Ther"},{"key":"10.1038\/mt.2015.49_bib31","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/cgt.2013.26","article-title":"Inhibitors of C5 complement enhance vaccinia virus oncolysis","volume":"20","author":"Magge","year":"2013","journal-title":"Cancer Gene Ther"},{"key":"10.1038\/mt.2015.49_bib32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4049\/jimmunol.118.1.28","article-title":"Effect of selective complement deficiency on the rate of neutralization of enveloped viruses by human sera","volume":"118","author":"Leddy","year":"1977","journal-title":"J Immunol"},{"key":"10.1038\/mt.2015.49_bib33","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nature04721","article-title":"Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity","volume":"441","author":"Roberts","year":"2006","journal-title":"Nature"},{"key":"10.1038\/mt.2015.49_bib34","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1038\/mt.2011.92","article-title":"Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis","volume":"19","author":"Miest","year":"2011","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2015.49_bib35","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1182\/blood-2008-09-178459","article-title":"Human erythrocytes bind and inactivate type 5 adenovirus by presenting Coxsackie virus-adenovirus receptor and complement receptor 1","volume":"113","author":"Carlisle","year":"2009","journal-title":"Blood"},{"key":"10.1038\/mt.2015.49_bib36","doi-asserted-by":"crossref","first-page":"185ra63","DOI":"10.1126\/scitranslmed.3005361","article-title":"Oncolytic and immunotherapeutic vaccinia induces antibody-mediated complement-dependent cancer cell lysis in humans","volume":"5","author":"Kim","year":"2013","journal-title":"Sci Transl Med"},{"key":"10.1038\/mt.2015.49_bib37","first-page":"11","article-title":"Heterogeneous delivery is a barrier to the translational advancement of oncolytic virotherapy for treating solid tumors","volume":"6","author":"Miller","year":"2014","journal-title":"Virus Adapt Treat"},{"key":"10.1038\/mt.2015.49_bib38","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1093\/jnci\/djt305","article-title":"Enhanced tumor uptake and penetration of virotherapy using polymer stealthing and focused ultrasound","volume":"105","author":"Carlisle","year":"2013","journal-title":"J Natl Cancer Inst"},{"key":"10.1038\/mt.2015.49_bib39","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0022-1759(89)90088-4","article-title":"Mouse strains with typical mammalian levels of complement activity","volume":"125","author":"Ong","year":"1989","journal-title":"J Immunol Methods"},{"key":"10.1038\/mt.2015.49_bib40","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0161-5890(95)00135-2","article-title":"Mouse complement component C4 is devoid of classical pathway C5 convertase subunit activity","volume":"33","author":"Ebanks","year":"1996","journal-title":"Mol Immunol"},{"key":"10.1038\/mt.2015.49_bib41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.molimm.2014.06.003","article-title":"Inhibitor(s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica","volume":"62","author":"Ratelade","year":"2014","journal-title":"Mol Immunol"},{"key":"10.1038\/mt.2015.49_bib42","doi-asserted-by":"crossref","first-page":"11339","DOI":"10.1128\/JVI.01491-14","article-title":"Potent neutralization of vaccinia virus by divergent murine antibodies targeting a common site of vulnerability in L1 protein","volume":"88","author":"Kaever","year":"2014","journal-title":"J Virol"},{"key":"10.1038\/mt.2015.49_bib43","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.smim.2013.04.001","article-title":"Complement inhibition in cancer therapy","volume":"25","author":"Pio","year":"2013","journal-title":"Semin Immunol"},{"key":"10.1038\/mt.2015.49_bib44","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/ni.1655","article-title":"Modulation of the antitumor immune response by complement","volume":"9","author":"Markiewski","year":"2008","journal-title":"Nat Immunol"},{"key":"10.1038\/mt.2015.49_bib45","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/mt.2011.276","article-title":"The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers","volume":"20","author":"Parato","year":"2012","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2015.49_bib46","doi-asserted-by":"crossref","first-page":"6810","DOI":"10.1128\/JVI.00334-06","article-title":"ICP0 gene expression is a herpes simplex virus type 1 apoptotic trigger","volume":"80","author":"Sanfilippo","year":"2006","journal-title":"J Virol"},{"key":"10.1038\/mt.2015.49_bib47","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1089\/15368590252917610","article-title":"Identification of human mannose binding lectin (MBL) recognition sites for novel inhibitory antibodies","volume":"21","author":"Zhao","year":"2002","journal-title":"Hybrid Hybridomics"},{"key":"10.1038\/mt.2015.49_bib48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.molimm.2004.07.043","article-title":"A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice","volume":"42","author":"Thurman","year":"2005","journal-title":"Mol Immunol"},{"key":"10.1038\/mt.2015.49_bib49","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jim.2007.04.004","article-title":"Fluorochrome-linked immunoassay for functional analysis of the mannose binding lectin complement pathway to the level of C3 cleavage","volume":"323","author":"Walsh","year":"2007","journal-title":"J Immunol Methods"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616301344?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616301344?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:23:24Z","timestamp":1691540604000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001616301344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["S1525001616301344"],"URL":"https:\/\/doi.org\/10.1038\/mt.2015.49","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2015,6]]}}}