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http://dx.doi.org/10.25673/85384
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DC Field | Value | Language |
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dc.contributor.author | Voigt, Johanna | - |
dc.contributor.author | Meyer, Christoph | - |
dc.contributor.author | Bordusa, Frank | - |
dc.date.accessioned | 2022-05-05T07:46:12Z | - |
dc.date.available | 2022-05-05T07:46:12Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/87336 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/85384 | - |
dc.description.abstract | Bispecific antibodies (bsAbs) were first developed in the 1960s and are now emerging as a leading class of immunotherapies for cancer treatment with the potential to further improve clinical efficacy and safety. Many different formats of bsAbs have been established in the last few years, mainly generated genetically. Here we report on a novel, flexible, and fast chemo–enzymatic, as well as purely enzymatic strategies, for generating bispecific antibody fragments by covalent fusion of two functional antibody Fab fragments (Fabs). For the chemo–enzymatic approach, we first modified the single Fabs site-specifically with click anchors using an enhanced Trypsiligase variant (eTl) and afterward converted the modified Fabs into the final heterodimers via click chemistry. Regarding the latter, we used the strain-promoted alkyne-azide cycloaddition (SPAAC) and inverse electron-demand Diels–Alder reaction (IEDDA) click approaches well known for their fast reaction kinetics and fewer side reactions. For applications where the non-natural linkages or hydrophobic click chemistry products might interfere, we developed two purely enzymatic alternatives enabling C- to C- and C- to N-terminal coupling of the two Fabs via a native peptide bond. This simple system could be expanded into a modular system, eliminating the need for extensive genetic engineering. The bispecific Fab fragments (bsFabs) produced here to bind the growth factors ErbB2 and ErbB3 with similar KD values, such as the sole Fabs. Tested in breast cancer cell lines, we obtained biologically active bsFabs with improved properties compared to its single Fab counterparts. | eng |
dc.description.sponsorship | Publikationsfonds MLU | - |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject.ddc | 572 | - |
dc.title | Synthesis of multiple bispecific antibody formats with only one single enzyme based on enhanced trypsiligase | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | International journal of molecular sciences | - |
local.bibliographicCitation.volume | 23 | - |
local.bibliographicCitation.issue | 6 | - |
local.bibliographicCitation.publishername | Molecular Diversity Preservation International | - |
local.bibliographicCitation.publisherplace | Basel | - |
local.bibliographicCitation.doi | 10.3390/ijms23063144 | - |
local.openaccess | true | - |
local.accessrights.dnb | free | - |
Appears in Collections: | Open Access Publikationen der MLU |
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File | Description | Size | Format | |
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ijms-23-03144.pdf | 5.63 MB | Adobe PDF | ![]() View/Open |