{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:52:01Z","timestamp":1753883521546,"version":"3.41.2"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T00:00:00Z","timestamp":1480464000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T00:00:00Z","timestamp":1480464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T00:00:00Z","timestamp":1480464000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["9420056","9522771","9902020","0094016"],"award-info":[{"award-number":["9420056","9522771","9902020","0094016"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41 RR000570","P41 RR002301"],"award-info":[{"award-number":["P41 RR000570","P41 RR002301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Specific aim<\/jats:title><jats:p>The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination\u2010induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients\u2019 informed consent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>By biomolecular engineering, we have created a novel family of biomolecules: antibody \u00d7 vaccine engineered constructs (AVEC: anti\u2010HER\u20102 \u00d7 HBsAg). We have collected the blood from the volunteers, and measured the titers of anti\u2010HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER\u20102 over\u2010expressing epithelial ovarian cancers: OV\u201090, TOC\u2010112D, SKOV\u20103, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER\u20102+ ovarian cancer cells with AVEC: anti\u2010HER\u20102 \u00d7 HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti\u2010HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti\u2010HER\u20102 antibodies alone and\/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Herein, we report attaining the great improvement in eradication efficacy of ovarian epithelial cancer cells\u2019 by engaging prophylactic immunity against HBV; thus creating a novel paradigm for immunotherapy of ovarian cancer. We have accomplished that by designing, synthesis, and administration of AVEC. Therefore, the HBV vaccination acquired immunity mounts immune response against the vaccine, but AVEC redirect, accelerate, and amplify this immune response of all the elements of the native and adaptive immune system against ovarian cancer. Our novel paradigm of immunotherapy is currently streamlined to clinical trials also of other cancers, while also engaging prophylactic and acquired immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Novel antibody\u2010vaccine engineered constructs (AVEC) create the solid foundation for redirected, accelerated, and amplified prophylactic, HBV vaccination\u2010induced immunity immunotherapy (RAAVIIT) of ovarian cancers.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s40169-016-0125-2","type":"journal-article","created":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T16:32:59Z","timestamp":1480523579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel paradigm for immunotherapy of ovarian cancer by engaging prophylactic immunity against hepatitis B virus"],"prefix":"10.1002","volume":"5","author":[{"given":"Marek","family":"Malecki","sequence":"first","affiliation":[{"name":"National Magnetic Resonance Facility National Institutes of Health Madison WI USA"},{"name":"Phoenix Biomolecular Engineering Foundation San Francisco CA USA"},{"name":"University of Wisconsin Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Putzer","sequence":"additional","affiliation":[{"name":"District of Columbia Department of Health Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Quach","sequence":"additional","affiliation":[{"name":"Long Island University Brookville NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaitanya","family":"Dodivenaka","sequence":"additional","affiliation":[{"name":"South Dakota State University Brookings SD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xenia","family":"Tombokan","sequence":"additional","affiliation":[{"name":"Bruker Bio\u2010Spin Corporation The Woodlands TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318264f794"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5468\/ogs.2015.58.2.124"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2470152"},{"issue":"13","key":"e_1_2_8_5_1","first-page":"4087","article-title":"Overexpression of HER\u20102\/neu is associated with poor survival in advanced epithelial ovarian cancer","volume":"50","author":"Berchuck A","year":"1990","journal-title":"Cancer Res"},{"issue":"11","key":"e_1_2_8_6_1","first-page":"667","article-title":"Overexpression of c\u2010erbB\u20102 oncogene in primary ovarian cancers: incidence and prognostic significance in 243 patients","volume":"52","author":"Meden H","year":"1992","journal-title":"Geburtshilfe Frauenheilkd"},{"key":"e_1_2_8_7_1","first-page":"2420","article-title":"Overexpression of HER\u20102 in ovarian carcinomas","volume":"61","author":"Hellstrom I","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049829"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2011.11.044"},{"key":"e_1_2_8_10_1","unstructured":"Trastuzumab.http:\/\/www.fda.gov\/drugs\/developmentapprovalprocess\/howdrugsaredevelopedandapproved\/approvalapplications\/therapeuticbiologicapplications\/ucm080591.htm. Accessed 1 Sept 2016"},{"key":"e_1_2_8_11_1","unstructured":"Pertuzumab.http:\/\/www.fda.gov\/safety\/medwatch\/safetyinformation\/safetyalertsforhumanmedicalproducts\/ucm350817.htm. Accessed 1 Sept 2016"},{"key":"e_1_2_8_12_1","first-page":"128","article-title":"Treatment of HER2\u2010positive ovarian cancer","volume":"23","author":"Figueroa M","year":"2014","journal-title":"Ovarian"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1100"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr045001"},{"key":"e_1_2_8_15_1","first-page":"1","article-title":"Surveillance for acute viral hepatitis\u2014United States, 2007","volume":"58","author":"Daniels D","year":"2007","journal-title":"Morb Mortal Wkly Rep Surveill Summ"},{"key":"e_1_2_8_16_1","unstructured":"EngerixB.http:\/\/www.fda.gov\/biologicsbloodvaccines\/vaccines\/approvedproducts\/ucm398332.htm. Accessed 1 Sept 2016"},{"key":"e_1_2_8_17_1","unstructured":"Recombivaxhttp:\/\/www.fda.gov\/biologicsbloodvaccines\/vaccines\/approvedproducts\/ucm376931.htm. Accessed 1 Sept 2016"},{"key":"e_1_2_8_18_1","unstructured":"OV\u201090 (CRL\u201011732)http:\/\/www.atcc.org\/Products\/All\/CRL\u201011732.aspx. Accessed 1 Sept 2016"},{"key":"e_1_2_8_19_1","unstructured":"TOV\u2010112D (CRL\u201011731)http:\/\/www.atcc.org\/Products\/All\/CRL\u201011731.aspx. Accessed 1 Sept 2016"},{"key":"e_1_2_8_20_1","unstructured":"OVCAR\u20103 (HTB\u2010161)http:\/\/www.atcc.org\/Products\/All\/HTB\u2010161.aspx. Accessed 1 Sept 2016"},{"key":"e_1_2_8_21_1","unstructured":"SKOV\u20103 (HTB\u201077)http:\/\/www.atcc.org\/Products\/All\/HTB\u201077.aspx. Accessed 1 Sept 2016"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261567298"},{"key":"e_1_2_8_23_1","unstructured":"IgGLC.http:\/\/www.imgt.org\/3Dstructure\u2010DB\/cgi\/details.cgi?pdbcode=7637&Part=Chain&Chain=7637L. Accessed 1 Sept 2016"},{"key":"e_1_2_8_24_1","unstructured":"IgGHC.http:\/\/www.imgt.org\/3Dstructure\u2010DB\/cgi\/details.cgi?pdbcode=7637&Part=Chain&Chain=7637H. Accessed 1 Sept 2016"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/280815a0"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/298347a0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2002.30806.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a131053"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00145-7"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2009.01272.x"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1186\/s40169-016-0125-2","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40169-016-0125-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1186%2Fs40169-016-0125-2","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1186\/s40169-016-0125-2","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1186%2Fs40169-016-0125-2","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1186\/s40169-016-0125-2","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40169-016-0125-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1186\/s40169-016-0125-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T07:09:30Z","timestamp":1693984170000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1186\/s40169-016-0125-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,30]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1186\/s40169-016-0125-2"],"URL":"https:\/\/doi.org\/10.1186\/s40169-016-0125-2","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"type":"print","value":"2001-1326"},{"type":"electronic","value":"2001-1326"}],"subject":[],"published":{"date-parts":[[2016,11,30]]},"article-number":"e44"}}