Abstract
The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in the treatment of cancer. RITs result from the fusion of antibodies to toxin proteins for targeting and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibition of multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system. This paper is devoted to review recent advances in the design of immunotoxins with lower immunogenicity.
Keywords: Recombinant immunotoxin, toxins, immunogenicity, immunosuppressive therapy, anti-drug antibodies, humanization, fragment.
[http://dx.doi.org/10.1146/annurev.med.58.070605.115320] [PMID: 17059365]
[http://dx.doi.org/10.1016/j.xphs.2019.10.037] [PMID: 31669121]
[http://dx.doi.org/10.1080/08830185.2017.1284211] [PMID: 28282218]
[http://dx.doi.org/10.1016/j.imlet.2016.10.008] [PMID: 27984065]
[http://dx.doi.org/10.3390/toxins5081486] [PMID: 23965432]
[PMID: 16709020]
[http://dx.doi.org/10.2174/1381612820666140826153913] [PMID: 25341935]
[http://dx.doi.org/10.1111/imr.12390] [PMID: 26864110]
[http://dx.doi.org/10.1111/j.1742-4658.2011.08182.x] [PMID: 21585657]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0089-T] [PMID: 24928849]
[http://dx.doi.org/10.1016/j.ajpath.2018.04.016] [PMID: 29870741]
[http://dx.doi.org/10.1073/pnas.83.5.1320] [PMID: 3006045]
[http://dx.doi.org/10.1128/IAI.15.1.138-144.1977] [PMID: 188760]
[http://dx.doi.org/10.3390/biomedicines5020028] [PMID: 28574434]
[http://dx.doi.org/10.1146/annurev.mi.44.100190.002003] [PMID: 2123620]
[http://dx.doi.org/10.1517/14712598.6.8.787] [PMID: 16856800]
[http://dx.doi.org/10.1038/s41375-018-0210-1] [PMID: 30030507]
[http://dx.doi.org/10.1080/14712598.2019.1614558] [PMID: 31045462]
[http://dx.doi.org/10.1016/j.ejphar.2020.172912] [PMID: 31926992]
[http://dx.doi.org/10.1016/j.jsbmb.2020.105651] [PMID: 32147458]
[http://dx.doi.org/10.1002/pro.5560030912] [PMID: 7833808]
[http://dx.doi.org/10.3389/fmicb.2019.02340] [PMID: 31681205]
[http://dx.doi.org/10.3390/toxins2112519] [PMID: 22069564]
[http://dx.doi.org/10.1016/j.bcp.2017.04.009] [PMID: 28408344]
[PMID: 30609921]
[http://dx.doi.org/10.1016/j.jim.2017.05.008] [PMID: 28551309]
[http://dx.doi.org/10.1073/pnas.1815087116] [PMID: 30718426]
[http://dx.doi.org/10.1007/s40265-019-01087-z] [PMID: 30859413]
[http://dx.doi.org/10.1016/j.cellimm.2017.01.003] [PMID: 28087047]
[http://dx.doi.org/10.1016/j.pep.2016.06.001] [PMID: 27298212]
[http://dx.doi.org/10.1016/j.ymeth.2005.01.001] [PMID: 15848070]
[http://dx.doi.org/10.4161/mabs.2.3.11641]
[http://dx.doi.org/10.1016/S0167-7799(00)88912-X] [PMID: 7766222]
[http://dx.doi.org/10.1002/biot.200900218] [PMID: 20069580]
[http://dx.doi.org/10.1200/JCO.2000.18.8.1622] [PMID: 10764422]
[http://dx.doi.org/10.1073/pnas.140210597] [PMID: 10890891]
[http://dx.doi.org/10.1021/bc060314x] [PMID: 17346030]
[http://dx.doi.org/10.1039/C9CP04387J] [PMID: 31720639]
[http://dx.doi.org/10.1158/1535-7163.MCT-19-0890] [PMID: 31871266]
[http://dx.doi.org/10.3390/biomedicines6020072] [PMID: 29925790]
[http://dx.doi.org/10.1111/j.1349-7006.2009.01192.x] [PMID: 19459847]
[PMID: 22593247]
[PMID: 2212674]
[http://dx.doi.org/10.4049/jimmunol.173.6.3801] [PMID: 15356127]
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0554] [PMID: 18790773]
[PMID: 14578460]
[http://dx.doi.org/10.1016/j.canlet.2016.02.020] [PMID: 26912070]
[http://dx.doi.org/10.3390/antib2010019]
[http://dx.doi.org/10.1080/2162402X.2019.1641392] [PMID: 31646080]
[http://dx.doi.org/10.18632/oncotarget.26618] [PMID: 30783518]
[http://dx.doi.org/10.3390/vaccines6040076] [PMID: 30463297]
[http://dx.doi.org/10.1021/bi00341a030] [PMID: 4074709]
[http://dx.doi.org/10.1021/bi00360a008] [PMID: 2424496]
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3717] [PMID: 15256457]
[http://dx.doi.org/10.1080/10428190701272264] [PMID: 17577782]
[http://dx.doi.org/10.1182/blood-2007-04-082768] [PMID: 18230757]
[PMID: 28039694]
[http://dx.doi.org/10.1097/CJI.0b013e3181cd1164]
[http://dx.doi.org/10.1182/blood-2008-08-173195] [PMID: 18988862]
[http://dx.doi.org/10.4049/jimmunol.177.12.8822] [PMID: 17142785]
[http://dx.doi.org/10.1073/pnas.1209292109] [PMID: 22753489]
[PMID: 11948105]
[http://dx.doi.org/10.1073/pnas.1102746108] [PMID: 21436054]
[http://dx.doi.org/10.1016/j.leukres.2014.06.014] [PMID: 25127689]
[http://dx.doi.org/10.1200/JCO.2008.20.2630] [PMID: 19414673]
[http://dx.doi.org/10.1007/s40265-018-1000-9] [PMID: 30357593]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1456] [PMID: 19188153]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0132] [PMID: 25239937]
[http://dx.doi.org/10.4049/jimmunol.172.11.6658] [PMID: 15153481]
[http://dx.doi.org/10.1016/S0065-2776(00)75004-8] [PMID: 10879284]
[http://dx.doi.org/10.1046/j.1365-3083.1996.d01-336.x] [PMID: 8947599]
[http://dx.doi.org/10.1073/pnas.1014739108] [PMID: 21209329]
[http://dx.doi.org/10.1097/CJI.0b013e3181a6981c] [PMID: 19483652]
[http://dx.doi.org/10.1016/j.jim.2015.06.003] [PMID: 26056938]
[http://dx.doi.org/10.1073/pnas.1218138109] [PMID: 23213206]
[http://dx.doi.org/10.1073/pnas.1405153111] [PMID: 24799704]
[http://dx.doi.org/10.1158/1535-7163.MCT-17-1041] [PMID: 29695631]
[http://dx.doi.org/10.1074/jbc.RA118.006704] [PMID: 30683694]