{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:46:04Z","timestamp":1789735564515,"version":"4.0.1"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0087240","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T23:49:43Z","timestamp":1390520983000},"page":"e87240","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":53,"title":["A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma"],"prefix":"10.1371","volume":"9","author":[{"given":"Sergio","family":"Arancibia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabi\u00e1n","family":"Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Del Campo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Tampe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Ying","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"De Ioannes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Moltedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed C.","family":"Lavelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Manubens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo E.","family":"De Ioannes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda In\u00e9s","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,1,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/0264-410X(95)00011-O","article-title":"Adjuvants for human vaccines\u2014current status, problems and future prospects","volume":"13","author":"RK Gupta","year":"1995","journal-title":"Vaccine"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/j.0818-9641.2004.01272.x","article-title":"Vaccine adjuvants: Current state and future trends","volume":"82","author":"N Petrovsky","year":"2004","journal-title":"Immunol Cell Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nrmicro1681","article-title":"The perfect mix: recent progress in adjuvant research","volume":"5","author":"B Guy","year":"2007","journal-title":"Nat Rev Microbiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1016\/j.vaccine.2008.06.098","article-title":"Evaluation of widely consumed botanicals as immunological adjuvants","volume":"26","author":"G Ragupathi","year":"2008","journal-title":"Vaccine"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1038\/nm1210","article-title":"Targeting the innate immune response with improved vaccine adjuvants","volume":"11","author":"A Pashine","year":"2005","journal-title":"Nat Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1440-1711.2005.01350.x","article-title":"Carbohydrate vaccines as immunotherapy for cancer","volume":"83","author":"SF Slovin","year":"2005","journal-title":"Immunol Cell Biol"},{"key":"ref7","first-page":"236","article-title":"Hemocyanins as immunostimulants","volume":"139","author":"M Del Campo","year":"2011","journal-title":"Rev Med Chil"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Arancibia S, Salazar F, Becker M (2012) Hemocyanins in the Immunotherapy of Superficial Bladder Cancer. Janeza, Croatia: INTECH.","DOI":"10.5772\/28281"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1200\/JCO.2011.39.2936","article-title":"Intracutaneous and intravesical immunotherapy with keyhole limpet hemocyanin compared with intravesical mitomycin in patients with non-muscle-invasive bladder cancer: Results from a prospective randomized phase III trial","volume":"30","author":"RJ Lammers","year":"2012","journal-title":"J Clin Oncol"},{"key":"ref10","first-page":"3315","article-title":"Augmenting the immunogenicity of synthetic MUC1 peptide vaccines in mice","volume":"56","author":"S Zhang","year":"1996","journal-title":"Cancer Res"},{"key":"ref11","first-page":"2618","article-title":"Enhancement of tumor lysate- and peptide-pulsed dendritic cell-based vaccines by the addition of foreign helper protein","volume":"61","author":"K Shimizu","year":"2001","journal-title":"Cancer Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"4987","DOI":"10.1158\/0008-5472.CAN-04-0252","article-title":"A fully synthetic therapeutic vaccine candidate targeting carcinoma-associated Tn carbohydrate antigen induces tumor-specific antibodies in nonhuman primates","volume":"64","author":"R Lo-Man","year":"2004","journal-title":"Cancer Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.molimm.2007.07.020","article-title":"Keyhole limpet hemocyanin induces the activation and maturation of human dendritic cells through the involvement of mannose receptor","volume":"45","author":"P Presicce","year":"2008","journal-title":"Mol Immunol"},{"key":"ref14","first-page":"13","article-title":"Negative staining of thinly spread biological particulates","volume":"117","author":"JR Harris","year":"1999","journal-title":"Methods Mol Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"R20","DOI":"10.1007\/BF01470995","article-title":"Keyhole limpet hemocyanin conjugate vaccines against cancer: The Memorial Sloan Kettering experience","volume":"127","author":"C Musselli","year":"2001","journal-title":"J Cancer Res Clin Oncol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/0305-0491(95)02091-8","article-title":"Keyhole limpet hemocyanin: Structural and functional characterization of two different subunits and multimers","volume":"113","author":"RD Swerdlow","year":"1996","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1006\/abbi.1999.1478","article-title":"Hemocyanin subunit organization of the gastropod <italic>Rapana thomasiana<\/italic>","volume":"372","author":"W Gebauer","year":"1999","journal-title":"Arch Biochem Biophys"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.intimp.2008.03.008","article-title":"Modulation of the immune response using <italic>Rapana thomasiana<\/italic> hemocyanin","volume":"8","author":"A Tchorbanov","year":"2008","journal-title":"Int Immunopharmacol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1080\/08820130802403366","article-title":"Immunological potential of <italic>Helix vulgaris<\/italic> and <italic>Rapana venosa<\/italic> hemocyanins","volume":"37","author":"P Dolashka-Angelova","year":"2008","journal-title":"Immunol Invest"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1016\/j.juro.2006.07.136","article-title":"Immunotherapeutic effect of <italic>Concholepas<\/italic> hemocyanin in the murine bladder cancer model: Evidence for conserved antitumor properties among hemocyanins","volume":"176","author":"B Moltedo","year":"2006","journal-title":"J Urol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-3233(08)60545-8","article-title":"Hemocyanins","volume":"47","author":"KE van Holde","year":"1995","journal-title":"Adv Protein Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/icb\/icm063","article-title":"Minireview: Recent progress in hemocyanin research","volume":"47","author":"H Decker","year":"2007","journal-title":"Integr Comp Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"26134","DOI":"10.1074\/jbc.M400903200","article-title":"Hemocyanin of the molluscan <italic>Concholepas concholepas<\/italic> exhibits an unusual heterodecameric array of subunits","volume":"279","author":"P De Ioannes","year":"2004","journal-title":"J Biol Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s10895-008-0338-x","article-title":"Spectroscopic properties and conformational stability of <italic>Concholepas concholepas<\/italic> hemocyanin","volume":"18","author":"K Idakieva","year":"2008","journal-title":"J Fluoresc"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/eji.201142011","article-title":"Enhanced structural stability of <italic>Concholepas<\/italic> hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects","volume":"42","author":"S Arancibia","year":"2012","journal-title":"Eur J Immunol"},{"key":"ref26","first-page":"51","article-title":"Immunochemical and immunogenic properties of a purified keyhole limpet haemocyanin","volume":"22","author":"H Herskowitz","year":"1972","journal-title":"Immunology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.intimp.2008.12.011","article-title":"Immunodominant role of CCHA subunit of <italic>Concholepas<\/italic> hemocyanin is associated with unique biochemical properties","volume":"9","author":"MI Becker","year":"2009","journal-title":"Int Immunopharmacol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"UK Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1089\/153685902761022715","article-title":"Monoclonal antibodies to molluskan hemocyanin from <italic>Concholepas concholepas<\/italic> demonstrate common and specific epitopes among subunits","volume":"21","author":"H Oliva","year":"2002","journal-title":"Hybrid Hybridomics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/bj0390507","article-title":"The free amino groups of insulin","volume":"39","author":"F Sanger","year":"1945","journal-title":"Biochem J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/sj.jidsymp.5650024","article-title":"Analysis of immune cell infiltrates during squamous carcinoma development","volume":"11","author":"SR Junankar","year":"2006","journal-title":"J Investig Dermatol Symp Proc"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0022-1759(98)00204-X","article-title":"An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow","volume":"223","author":"MB Lutz","year":"1999","journal-title":"J Immunol Methods"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.micron.2003.10.007","article-title":"Structural subunit organization of molluscan hemocyanins","volume":"35","author":"M Paccagnella","year":"2004","journal-title":"Micron"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.bbrc.2007.07.098","article-title":"Involvement of glycan chains in the antigenicity of <italic>Rapana thomasiana<\/italic> hemocyanin","volume":"361","author":"NI Siddiqui","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.jmb.2008.10.080","article-title":"Keyhole limpet hemocyanin: 9-A CryoEM structure and molecular model of the KLH1 didecamer reveal the interfaces and intricate topology of the 160 functional units","volume":"385","author":"C Gatsogiannis","year":"2009","journal-title":"J Mol Biol"},{"key":"ref36","first-page":"307","article-title":"Keyhole limpet hemocyanin contains Gal(beta 1-3)-GalNAc determinants that are cross-reactive with the T antigen","volume":"40","author":"I Wirguin","year":"1995","journal-title":"Cancer Immunol Immunother"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1046\/j.1432-1033.2002.03244.x","article-title":"Hemocyanin from the keyhole limpet <italic>Megathura crenulata<\/italic> (KLH) carries a novel type of N-glycans with Gal(beta1-6)Man-motifs","volume":"269","author":"T Kurokawa","year":"2002","journal-title":"Eur J Biochem"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Ponder WF, Lindberg DR, editors (2008) Phylogeny and Evolution of the Mollusca. Berkeley: University of California Press.","DOI":"10.1525\/california\/9780520250925.001.0001"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"732","DOI":"10.4049\/jimmunol.106.3.732","article-title":"Genetic control of the immune response of mice to hemocyanin. I. The role of macrophages","volume":"106","author":"JC Cerottini","year":"1971","journal-title":"J Immunol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1471-2172-4-5","article-title":"Genetic control of the innate immune response","volume":"4","author":"CA Wells","year":"2003","journal-title":"BMC Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.amjsurg.2007.08.005","article-title":"Keyhole limpet hemocyanin: An effective adjunct against melanoma in vivo","volume":"194","author":"I Rizvi","year":"2007","journal-title":"Am J Surg"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1200\/JCO.2003.08.099","article-title":"Intravesical therapy for superficial bladder cancer: Slow but steady progress","volume":"21","author":"DL Lamm","year":"2003","journal-title":"J Clin Oncol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1084\/jem.20052442","article-title":"Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis","volume":"203","author":"L Delamarre","year":"2006","journal-title":"J Exp Med"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"J Banchereau","year":"1998","journal-title":"Nature"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1177\/1753425912449549","article-title":"Dendritic cells and their role in tumor immunosurveillance","volume":"19","author":"M Strioga","year":"2013","journal-title":"Innate Immun"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.3181\/0702-MR-42","article-title":"A comparison and critical analysis of preclinical anticancer vaccination strategies","volume":"232","author":"JN Kochenderfer","year":"2007","journal-title":"Exp Biol Med (Maywood)"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.bbrc.2008.04.120","article-title":"A lectin recognizes differential arrangements of O-glycans on mucin repeats","volume":"371","author":"K Kato","year":"1972","journal-title":"Biochem Biophys Res Commun"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000052391","article-title":"Keyhole limpet hemocyanin immunotherapy of bladder cancer: Laboratory and clinical studies","volume":"37","author":"DL Lamm","year":"2000","journal-title":"Eur Urol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S1359-6101(03)00043-1","article-title":"The biology of IL-12: Coordinating innate and adaptive immune responses","volume":"14","author":"WT Watford","year":"2003","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.4049\/jimmunol.181.5.3148","article-title":"The C-type lectin macrophage galactose-type lectin impedes migration of immature APCs","volume":"181","author":"SJ van Vliet","year":"2008","journal-title":"J Immunol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1182\/blood-2011-02-339812","article-title":"Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived beta-glucans","volume":"117","author":"C Qi","year":"2011","journal-title":"Blood"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1016\/j.vaccine.2005.05.007","article-title":"Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity","volume":"23","author":"JK Gathuru","year":"2005","journal-title":"Vaccine"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/S0264-410X(00)00195-X","article-title":"Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates","volume":"19","author":"SK Kim","year":"2000","journal-title":"Vaccine"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/S0264-410X(01)00451-0","article-title":"Comparison of antibody titers after immunization with monovalent or tetravalent KLH conjugate vaccines","volume":"20","author":"G Ragupathi","year":"2002","journal-title":"Vaccine"},{"key":"ref55","first-page":"725","article-title":"Surface enhanced Raman spectrum of nanometric molecular systems","volume":"50","author":"P Leyton","year":"2005","journal-title":"J Chil Chem Soc"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1146\/annurev.immunol.22.012703.104538","article-title":"Cell biology of antigen processing in vitro and in vivo","volume":"23","author":"ES Trombetta","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1159\/000473584","article-title":"Keyhole limpet hemocyanine can enhance the natural killer activity of patients with transitional cell carcinoma of the bladder","volume":"19","author":"LM Molto","year":"1991","journal-title":"Eur Urol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.4049\/jimmunol.136.10.3899","article-title":"The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: Direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells","volume":"136","author":"JJ Mule","year":"1986","journal-title":"J Immunol"},{"key":"ref59","first-page":"676198","article-title":"Natural killer cells in human cancer: From biological functions to clinical applications","volume":"2011","author":"EM Levy","year":"2011","journal-title":"J Biomed Biotechnol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"40731","DOI":"10.1074\/jbc.M505985200","article-title":"Identification and characterization of keyhole limpet hemocyanin N-glycans mediating cross-reactivity with Schistosoma mansoni","volume":"280","author":"H Geyer","year":"2005","journal-title":"J Biol Chem"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0087240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:34:27Z","timestamp":1688949267000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0087240"}},"subtitle":[],"editor":[{"given":"Fabrizio","family":"Mattei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,1,23]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0087240","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,23]]}}}