{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:36:26Z","timestamp":1791308186036,"version":"4.3.1"},"reference-count":89,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,2,10]],"date-time":"2016-02-10T00:00:00Z","timestamp":1455062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Recombinant immunotoxins (<jats:styled-content style=\"fixed-case\">RIT<\/jats:styled-content>s) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38\u2010kDa portion of <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>seudomonas<\/jats:italic> exotoxin A (<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>38). Because <jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. <jats:styled-content style=\"fixed-case\">RIT<\/jats:styled-content>s have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of <jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less\u2010immunogenic <jats:styled-content style=\"fixed-case\">RIT<\/jats:styled-content>s by identifying and removing T\u2010 and B\u2010cell epitopes to hide the <jats:styled-content style=\"fixed-case\">RIT<\/jats:styled-content> from the immune system.<\/jats:p>","DOI":"10.1111\/imr.12390","type":"journal-article","created":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T19:06:52Z","timestamp":1455217612000},"page":"152-164","source":"Crossref","is-referenced-by-count":100,"title":["Immunogenicity of therapeutic recombinant immunotoxins"],"prefix":"10.1111","volume":"270","author":[{"given":"Ronit","family":"Mazor","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Onda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Pastan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,10]]},"reference":[{"key":"e_1_2_24_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.3.11782"},{"key":"e_1_2_24_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3241"},{"key":"e_1_2_24_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011931"},{"key":"e_1_2_24_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2009.03.012"},{"key":"e_1_2_24_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.6.8.787"},{"key":"e_1_2_24_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107263450402"},{"key":"e_1_2_24_8_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306139"},{"key":"e_1_2_24_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08182.x"},{"key":"e_1_2_24_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0089-T"},{"key":"e_1_2_24_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.2630"},{"key":"e_1_2_24_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2980"},{"key":"e_1_2_24_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209788923949"},{"key":"e_1_2_24_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.12.2095"},{"key":"e_1_2_24_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0396-350"},{"key":"e_1_2_24_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0801"},{"key":"e_1_2_24_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib1010039"},{"key":"e_1_2_24_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.8.1622"},{"key":"e_1_2_24_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0487"},{"key":"e_1_2_24_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.1756"},{"key":"e_1_2_24_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01181.x"},{"key":"e_1_2_24_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.12.3457.bloodjournal85123457"},{"key":"e_1_2_24_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4919"},{"key":"e_1_2_24_24_1","first-page":"313","article-title":"A Phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscle\u2010invasive bladder cancer in BCGrefractory and BCG\u2010intolerant patients","volume":"4","author":"Kowalski M","year":"2010","journal-title":"Drug Des Devel Ther"},{"key":"e_1_2_24_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02700027"},{"key":"e_1_2_24_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BREA.0000004371.48757.19"},{"key":"e_1_2_24_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.437"},{"key":"e_1_2_24_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28875"},{"key":"e_1_2_24_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0062"},{"key":"e_1_2_24_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.136"},{"key":"e_1_2_24_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(97)00011-4"},{"key":"e_1_2_24_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0132"},{"key":"e_1_2_24_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pai.00000141545.36485.d6"},{"key":"e_1_2_24_34_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520611313020014"},{"key":"e_1_2_24_35_1","volume-title":"Molecular Biology of the Cell","author":"Alberts B","year":"2002"},{"key":"e_1_2_24_36_1","unstructured":"OwenJA PuntJ StranfordSA JonesPP KubyJ.Kuby Immunol.New York:W.H. Freeman and Company 2013."},{"key":"e_1_2_24_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.001555"},{"key":"e_1_2_24_38_1","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1182\/asheducation.V2012.1.660.3798659","article-title":"Immunoconjugates and new molecular targets in hairy cell leukemia","volume":"2012","author":"Kreitman RJ","year":"2012","journal-title":"Hematology"},{"key":"e_1_2_24_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006941"},{"key":"e_1_2_24_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1160-3"},{"key":"e_1_2_24_41_1","article-title":"Complete remissions of adult T\u2010cell leukemia with anti\u2010CD25 recombinant immunotoxin LMB\u20102 and chemotherapy to block immunogenicity","author":"Kreitman RJ","year":"2015","journal-title":"Clin Cancer Res"},{"key":"e_1_2_24_42_1","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.4049\/jimmunol.159.10.5168","article-title":"Prevention of immunotoxin\u2010induced immunogenicity by coadministration with CTLA4Ig enhances antitumor efficacy","volume":"159","author":"Siegall CB","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_24_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400063"},{"key":"e_1_2_24_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2258"},{"key":"e_1_2_24_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402324"},{"key":"e_1_2_24_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.12051"},{"key":"e_1_2_24_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2014.06.014"},{"key":"e_1_2_24_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2009.07.014"},{"key":"e_1_2_24_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(00)88912-X"},{"key":"e_1_2_24_50_1","doi-asserted-by":"crossref","first-page":"7610","DOI":"10.1016\/S0021-9258(17)37331-3","article-title":"Pseudomonas exotoxin A mutants. Replacement of surface exposed residues in domain II with cysteine residues that can be modified with polyethylene glycol in a site\u2010specific manner","volume":"269","author":"Kuan CT","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_24_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36846-1"},{"key":"e_1_2_24_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140210597"},{"key":"e_1_2_24_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270624"},{"key":"e_1_2_24_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.62.11.5055-5065.1994"},{"key":"e_1_2_24_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8822"},{"key":"e_1_2_24_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804851105"},{"key":"e_1_2_24_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-173195"},{"key":"e_1_2_24_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181cd1164"},{"key":"e_1_2_24_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209292109"},{"key":"e_1_2_24_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8044-y"},{"key":"e_1_2_24_61_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0358"},{"key":"e_1_2_24_62_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-05-0189"},{"key":"e_1_2_24_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014739108"},{"key":"e_1_2_24_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.11.010"},{"key":"e_1_2_24_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181a6981c"},{"key":"e_1_2_24_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25554"},{"key":"e_1_2_24_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2009.01.009"},{"key":"e_1_2_24_68_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3187"},{"key":"e_1_2_24_69_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6658"},{"key":"e_1_2_24_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.03.544"},{"key":"e_1_2_24_71_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000405"},{"key":"e_1_2_24_72_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218138109"},{"key":"e_1_2_24_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2005.07.014"},{"key":"e_1_2_24_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405153111"},{"key":"e_1_2_24_75_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321126111"},{"key":"e_1_2_24_76_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-15-0532"},{"key":"e_1_2_24_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.91"},{"key":"e_1_2_24_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.06.003"},{"key":"e_1_2_24_79_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1102746108"},{"key":"e_1_2_24_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745-7580-6-6"},{"key":"e_1_2_24_81_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1843"},{"key":"e_1_2_24_82_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2530"},{"key":"e_1_2_24_83_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115582"},{"key":"e_1_2_24_84_1","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.4049\/jimmunol.143.8.2663","article-title":"I\u2010Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody\u2010binding regions of the HA1 subunit","volume":"143","author":"Barnett BC","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_24_85_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065748"},{"key":"e_1_2_24_86_1","first-page":"2311","article-title":"Hepatotoxicity in cancer patients receiving erb\u201038, a recombinant immunotoxin that targets the erbB2 receptor","volume":"5","author":"Pai\u2010Scherf LH","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_24_87_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1264"},{"key":"e_1_2_24_88_1","first-page":"3092","article-title":"A phase I trial of the single\u2010chain immunotoxin SGN\u201010 (BR96 sFv\u2010PE40) in patients with advanced solid tumors","volume":"8","author":"Posey JA","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_24_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000162782.86008.mL"},{"key":"e_1_2_24_90_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0869"}],"container-title":["Immunological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimr.12390","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimr.12390","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.12390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T11:56:33Z","timestamp":1694519793000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imr.12390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,10]]},"references-count":89,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/imr.12390"],"URL":"https:\/\/doi.org\/10.1111\/imr.12390","archive":["Portico"],"relation":{},"ISSN":["0105-2896","1600-065X"],"issn-type":[{"value":"0105-2896","type":"print"},{"value":"1600-065X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,10]]}}}