Abstract
Background and Aims: Antibody-based therapeutics have been shown to be promising for the treatment of colorectal cancer patients. However, the size and long-circulating half-lives of antibodies can limit their reproducible manufacture in clinical studies. Consequently, in novel therapeutic approaches, conventional antibodies are minimized and engineered to produce fragments like Fab, scFv, nanobody, bifunctional antibody, bispecific antibody, minibody, and diabody to preserve their high affinity and specificity to target pharmaceutical nanoparticle conjugates. This systematic review for the first time aimed to elucidate the role of various antibody fragments in colorectal cancer treatment.
Methods: A systematic literature search in the web of sciences, PubMed, Scopus, Google Scholar, and ProQuest was conducted. Reference lists of the articles were reviewed to identify the relevant papers. The full-text search included articles published in English during 19902021.
Results: Most of the 53 included studies were conducted in vitro and in most conducted studies singlechain antibodies were among the most used antibody fragments. Most antibodies targeted CEA in the treatment of colorectal cancer. Moreover, a large number of studies observed apoptosis induction and tumor growth inhibition. In addition, few studies implicated the role of the innate immune system as an indirect mechanism of tumor growth by enhancing NK-cell killing.
Conclusion: Antibody-based therapy was demonstrated to be of great promise in the treatment of colorectal cancer rather than common treatments such as radiotherapy, chemotherapy, and surgical operations. This type of specified cancer treatment can also induce the activation of the innate and specific immune systems to eradicate tumor cells.
Keywords: Antibody fragments, colorectal cancer, targeting, nanomedicine, immune system, Fab, scFV.
Graphical Abstract
[http://dx.doi.org/10.2147/DDDT.S119036] [PMID: 28138221]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[http://dx.doi.org/10.1016/j.ejmech.2014.10.072] [PMID: 25462264]
[http://dx.doi.org/10.1111/febs.13262] [PMID: 25752204]
[http://dx.doi.org/10.1089/cbr.2010.0899] [PMID: 21711100]
[http://dx.doi.org/10.1371/journal.pone.0192194] [PMID: 29420662]
[http://dx.doi.org/10.1002/ijc.2910610412] [PMID: 7759155]
[http://dx.doi.org/10.1016/j.lfs.2020.118791] [PMID: 33220288]
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3935] [PMID: 15087403]
[http://dx.doi.org/10.1142/S0219633617500699]
[http://dx.doi.org/10.5812/semj.45219]
[PMID: 9829586]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2651] [PMID: 29437789]
[http://dx.doi.org/10.15171/ijb.1472] [PMID: 29845054]
[PMID: 9829749]
[http://dx.doi.org/10.1016/j.biomaterials.2019.119231] [PMID: 31254933]
[http://dx.doi.org/10.1016/j.biopha.2017.12.033] [PMID: 29272788]
[http://dx.doi.org/10.1038/sj.bjc.6600423] [PMID: 12085265]
[http://dx.doi.org/10.1097/CJI.0000000000000086] [PMID: 26049545]
[http://dx.doi.org/10.1007/s11523-015-0391-8] [PMID: 26566946]
[http://dx.doi.org/10.1089/cbr.2012.1329] [PMID: 23611188]
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0026] [PMID: 30082472]
[http://dx.doi.org/10.1186/s40064-015-0943-5] [PMID: 25883890]
[http://dx.doi.org/10.1186/s12885-018-4989-y] [PMID: 30419845]
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0551] [PMID: 28904131]
[http://dx.doi.org/10.1016/S0196-9781(03)00049-4] [PMID: 12732332]
[http://dx.doi.org/10.1111/j.1365-2567.2006.02522.x] [PMID: 17343613]
[http://dx.doi.org/10.1016/j.yexcr.2020.112278] [PMID: 32918897]
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00210] [PMID: 32396000]
[PMID: 18360720]
[http://dx.doi.org/10.1016/j.tranon.2020.100916] [PMID: 33129108]
[http://dx.doi.org/10.3390/cancers12010054] [PMID: 31878090]
[http://dx.doi.org/10.3389/fonc.2020.571194] [PMID: 33392074]
[http://dx.doi.org/10.1002/cbin.10112] [PMID: 23576466]
[http://dx.doi.org/10.1007/s11816-020-00610-z]
[http://dx.doi.org/10.1021/bc0000379] [PMID: 11087333]
[http://dx.doi.org/10.1002/(SICI)1097-0142(19971215)80:12+<2618:AID-CNCR37>3.0.CO;2-D] [PMID: 9406716]
[http://dx.doi.org/10.1038/bjc.1994.338] [PMID: 8080740]
[http://dx.doi.org/10.1007/s00259-015-3254-8] [PMID: 26596724]
[http://dx.doi.org/10.18632/oncotarget.16930] [PMID: 28445134]
[http://dx.doi.org/10.1007/s12094-018-1886-4] [PMID: 29777377]
[http://dx.doi.org/10.1038/s41598-017-02483-9] [PMID: 28572590]
[http://dx.doi.org/10.1038/s41598-019-48285-z] [PMID: 31406218]
[http://dx.doi.org/10.1007/s11523-013-0290-9] [PMID: 23900680]
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0647] [PMID: 27037412]
[http://dx.doi.org/10.1007/s00280-018-3623-7] [PMID: 29926131]
[http://dx.doi.org/10.1074/jbc.M113.528109] [PMID: 24841203]
[http://dx.doi.org/10.1007/s00262-020-02667-9] [PMID: 32666260]
[http://dx.doi.org/10.1038/bjc.1996.555] [PMID: 8912535]
[PMID: 11156250]
[http://dx.doi.org/10.1016/j.bbrc.2020.03.071] [PMID: 32216966]
[http://dx.doi.org/10.1007/s00262-010-0892-3] [PMID: 20635083]
[http://dx.doi.org/10.1371/journal.pone.0095200] [PMID: 24736661]
[http://dx.doi.org/10.1038/sj.bjc.6605364] [PMID: 19953093]
[http://dx.doi.org/10.1016/j.biomaterials.2014.08.032] [PMID: 25212525]
[http://dx.doi.org/10.4161/19420862.2014.975660]
[http://dx.doi.org/10.1371/journal.pone.0036412] [PMID: 22574157]
[http://dx.doi.org/10.1200/JCO.2005.01.032] [PMID: 15466784]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2958] [PMID: 32345647]
[http://dx.doi.org/10.1158/2326-6066.CIR-16-0362] [PMID: 29615399]
[http://dx.doi.org/10.1089/hum.2018.229] [PMID: 30693795]
[http://dx.doi.org/10.1186/s40425-017-0222-9] [PMID: 28344808]