{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:29:19Z","timestamp":1773534559884,"version":"3.50.1"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007927","name":"University of Oklahoma Health Sciences Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","cancerletters.info","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2018,7]]},"DOI":"10.1016\/j.canlet.2018.03.027","type":"journal-article","created":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T19:34:34Z","timestamp":1521660874000},"page":"174-182","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["Anti-CD73 and anti-OX40 immunotherapy coupled with a novel biocompatible enzyme prodrug system for the treatment of recurrent, metastatic ovarian cancer"],"prefix":"10.1016","volume":"425","author":[{"given":"Needa A.","family":"Virani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elangovan","family":"Thavathiru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"McKernan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7606-8245","authenticated-orcid":false,"given":"Doris M.","family":"Benbrook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2401-627X","authenticated-orcid":false,"given":"Roger G.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2018.03.027_bib1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2353\/ajpath.2010.100105","article-title":"Ovarian cancer development and metastasis","volume":"177","author":"Lengyel","year":"2010","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.canlet.2018.03.027_bib2","doi-asserted-by":"crossref","DOI":"10.7603\/s40681-015-0019-4","article-title":"An overview of targeted cancer therapy","volume":"5","author":"Padma","year":"2015","journal-title":"Biomedicine"},{"key":"10.1016\/j.canlet.2018.03.027_bib3","first-page":"3314","article-title":"Strategies for enzyme\/prodrug cancer therapy","volume":"7","author":"Xu","year":"2001","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib4","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1158\/1078-0432.CCR-04-1645","article-title":"Antitumor effects of a monoclonal antibody that binds anionic phospholipids on the surface of tumor blood vessels in mice","volume":"11","author":"Ran","year":"2005","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib5","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/S0360-3016(02)03928-7","article-title":"Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy","volume":"54","author":"Ran","year":"2002","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"10.1016\/j.canlet.2018.03.027_bib6","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1158\/1535-7163.MCT-16-0263","article-title":"Antitumor synergism and enhanced survival with a tumor vasculature-targeted enzyme prodrug system, rapamycin, and cyclophosphamide","volume":"16","author":"Krais","year":"2017","journal-title":"Mol. Canc. Therapeut."},{"key":"10.1016\/j.canlet.2018.03.027_bib7","first-page":"85","article-title":"Annexin-directed \u03b2-glucuronidase for the targeted treatment of solid tumors, Protein Engineering","volume":"30","author":"Guillen","year":"2017","journal-title":"Des. Sel."},{"key":"10.1016\/j.canlet.2018.03.027_bib8","doi-asserted-by":"crossref","first-page":"035101","DOI":"10.1088\/1361-6528\/aa9c0c","article-title":"Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer","volume":"29","author":"Virani","year":"2017","journal-title":"Nanotechnology"},{"key":"10.1016\/j.canlet.2018.03.027_bib9","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1021\/cb300335j","article-title":"De novo engineering of a human cystathionine-\u03b3-lyase for systemic l-Methionine depletion cancer therapy","volume":"7","author":"Stone","year":"2012","journal-title":"ACS Chemical Biology"},{"key":"10.1016\/j.canlet.2018.03.027_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076403","article-title":"Purine Nucleoside Phosphorylase targeted by Annexin V to breast cancer vasculature for enzyme prodrug therapy","volume":"8","author":"Krais","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2018.03.027_bib11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/sj.cgt.7700587","article-title":"Methioninase gene therapy with selenomethionine induces apoptosis in bcl-2-overproducing lung cancer cells","volume":"10","author":"Yamamoto","year":"2003","journal-title":"Canc. Gene Ther."},{"key":"10.1016\/j.canlet.2018.03.027_bib12","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/jcp.21038","article-title":"Methylselenol generated from selenomethionine by methioninase downregulates integrin expression and induces caspase-mediated apoptosis of B16F10 melanoma cells","volume":"212","author":"Kim","year":"2007","journal-title":"J.\u00a0Cell. Physiol."},{"key":"10.1016\/j.canlet.2018.03.027_bib13","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/mc.10056","article-title":"Induction of caspase-mediated apoptosis and cell-cycle G1 arrest by selenium metabolite methylselenol","volume":"34","author":"Wang","year":"2002","journal-title":"Mol. Carcinog."},{"key":"10.1016\/j.canlet.2018.03.027_bib14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13048-015-0140-8","article-title":"A\u00a0metabolomic approach to identifying platinum resistance in ovarian cancer","volume":"8","author":"Poisson","year":"2015","journal-title":"J.\u00a0Ovarian Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib15","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.ctrv.2012.01.004","article-title":"A\u00a0review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension","volume":"38","author":"Cavuoto","year":"2012","journal-title":"Canc. Treat Rev."},{"key":"10.1016\/j.canlet.2018.03.027_bib16","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.canlet.2018.03.027_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: the cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"10.1016\/j.canlet.2018.03.027_bib18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ygyno.2016.05.007","article-title":"Ovarian cancer and the immune system\u2014the role of targeted therapies","volume":"142","author":"Turner","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"10.1016\/j.canlet.2018.03.027_bib19","doi-asserted-by":"crossref","first-page":"i11","DOI":"10.1093\/annonc\/mdw084","article-title":"Opportunities in immunotherapy of ovarian cancer","volume":"27","author":"Coukos","year":"2016","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.canlet.2018.03.027_bib20","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1158\/1078-0432.CCR-16-0224","article-title":"Dual faces of IFN\u03b3 in cancer progression: a role of PD-L1 induction in the determination of pro-and antitumor immunity","volume":"22","author":"Mandai","year":"2016","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib21","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1056\/NEJMoa020177","article-title":"Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer","volume":"348","author":"Zhang","year":"2003","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.canlet.2018.03.027_bib22","first-page":"1517","article-title":"TRANCE-and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients","volume":"9","author":"Schlienger","year":"2003","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ygyno.2011.09.039","article-title":"Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis","volume":"124","author":"Hwang","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"10.1016\/j.canlet.2018.03.027_bib24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40661-016-0033-6","article-title":"The role of immune checkpoint inhibition in the treatment of ovarian cancer","volume":"3","author":"Gaillard","year":"2016","journal-title":"Gynecol. Oncol. Res. Pract."},{"key":"10.1016\/j.canlet.2018.03.027_bib25","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1200\/JCO.2015.63.7785","article-title":"Targeting programmed cell death 1 in ovarian cancer","volume":"33","author":"Homicsko","year":"2015","journal-title":"J.\u00a0Clin. Oncol."},{"key":"10.1016\/j.canlet.2018.03.027_bib26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12929-017-0329-9","article-title":"Cancer immunotherapies targeting the PD-1 signaling pathway","volume":"24","author":"Iwai","year":"2017","journal-title":"J.\u00a0Biomed. Sci."},{"key":"10.1016\/j.canlet.2018.03.027_bib27","article-title":"PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer","volume":"9","author":"Guo","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.canlet.2018.03.027_bib28","doi-asserted-by":"crossref","first-page":"5626","DOI":"10.1158\/1078-0432.CCR-13-0545","article-title":"Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs","volume":"19","author":"Allard","year":"2013","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.trecan.2016.01.003","article-title":"Anti-CD73 in cancer immunotherapy: awakening new opportunities","volume":"2","author":"Antonioli","year":"2016","journal-title":"Trends Canc."},{"key":"10.1016\/j.canlet.2018.03.027_bib30","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2015.1127496","article-title":"CD73-adenosine reduces immune responses and survival in ovarian cancer patients","volume":"5","author":"Gaudreau","year":"2016","journal-title":"OncoImmunology"},{"key":"10.1016\/j.canlet.2018.03.027_bib31","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1158\/0008-5472.CAN-14-3569","article-title":"CD73 is associated with poor prognosis in high-grade serous ovarian cancer","volume":"75","author":"Turcotte","year":"2015","journal-title":"Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2015.00034","article-title":"OX40 agonists and combination immunotherapy: putting the pedal to the metal","volume":"5","author":"Linch","year":"2015","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2018.03.027_bib33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejca.2015.08.021","article-title":"Rationale for anti-OX40 cancer immunotherapy","volume":"52","author":"Aspeslagh","year":"2016","journal-title":"Eur. J. Canc."},{"key":"10.1016\/j.canlet.2018.03.027_bib34","doi-asserted-by":"crossref","first-page":"6673","DOI":"10.1158\/0008-5472.CAN-04-1822","article-title":"PEGylation confers greatly extended half-life and attenuated immunogenicity to recombinant methioninase in primates","volume":"64","author":"Yang","year":"2004","journal-title":"Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib35","first-page":"8377","article-title":"In\u00a0vivo efficacy of recombinant methioninase is enhanced by the combination of polyethylene glycol conjugation and pyridoxal 5\u2032-phosphate supplementation","volume":"63","author":"Sun","year":"2003","journal-title":"Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib36","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.1158\/0008-5472.CAN-16-1272","article-title":"CRISPR\/Cas9-mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high-grade serous carcinoma","volume":"76","author":"Walton","year":"2016","journal-title":"Canc. Res."},{"key":"10.1016\/j.canlet.2018.03.027_bib37","doi-asserted-by":"crossref","first-page":"26191","DOI":"10.1038\/srep26191","article-title":"Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing","volume":"6","author":"Cole","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.canlet.2018.03.027_bib38","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.canlet.2010.11.013","article-title":"Enzyme prodrug therapy designed to target L-methioninase to the tumor vasculature","volume":"301","author":"Van Rite","year":"2011","journal-title":"Canc. Lett."},{"key":"10.1016\/j.canlet.2018.03.027_bib39","unstructured":"G. Georgiou, E. Stone, W.-C. Lu, Engineered primate L-methioninase for therapeutic purposes, Google Patents, 2016, pp. U.S. Patent Application PCT\/US2014\/053359."},{"key":"10.1016\/j.canlet.2018.03.027_bib40","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2015.62.3397","article-title":"Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer","volume":"33","author":"Hamanishi","year":"2015","journal-title":"J.\u00a0Clin. Oncol."},{"key":"10.1016\/j.canlet.2018.03.027_bib41","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1073\/pnas.0611533104","article-title":"Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer","volume":"104","author":"Hamanishi","year":"2007","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.canlet.2018.03.027_bib42","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.4049\/jimmunol.1203194","article-title":"Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer","volume":"190","author":"Neyen","year":"2013","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.canlet.2018.03.027_bib43","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1158\/0008-5472.CAN-04-1406","article-title":"Circulating half-life of PEGylated recombinant methioninase holoenzyme is highly dose dependent on cofactor pyridoxal-5\u2032-phosphate","volume":"64","author":"Yang","year":"2004","journal-title":"Canc. Res."}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383518302246?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383518302246?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T22:55:05Z","timestamp":1534978505000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383518302246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":43,"alternative-id":["S0304383518302246"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2018.03.027","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Anti-CD73 and anti-OX40 immunotherapy coupled with a novel biocompatible enzyme prodrug system for the treatment of recurrent, metastatic ovarian cancer","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2018.03.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}