2022
DOI: 10.3390/ijms23063144
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Synthesis of Multiple Bispecific Antibody Formats with Only One Single Enzyme Based on Enhanced Trypsiligase

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 Fa… Show more

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Cited by 2 publications
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“…These BsAb constructs function by forming a transient direct immune synapse between T cells and cells expressing the target antigen of choice (8), bypassing normal interactions between the T cell receptor (TCR) and antigen-presenting major histocompatibility complex (MHC) molecules to induce robust polyclonal cytotoxic T cell activation and consequent cytolytic tumor clearance. The establishment of novel approaches to generating a diverse array of BsAbs has the potential to further extend the clinical utility of these molecules (9), underscoring the need for further efforts to understand and optimize their activity.…”
Section: Introductionmentioning
confidence: 99%
“…These BsAb constructs function by forming a transient direct immune synapse between T cells and cells expressing the target antigen of choice (8), bypassing normal interactions between the T cell receptor (TCR) and antigen-presenting major histocompatibility complex (MHC) molecules to induce robust polyclonal cytotoxic T cell activation and consequent cytolytic tumor clearance. The establishment of novel approaches to generating a diverse array of BsAbs has the potential to further extend the clinical utility of these molecules (9), underscoring the need for further efforts to understand and optimize their activity.…”
Section: Introductionmentioning
confidence: 99%
“…Furthermore, numerous different bsAbs have been documented in the last decade, mainly generated genetically. Bordusa et al [ 16 ] published a novel chemo-enzymatic protocol for generating bsAbs fragments through the covalent fusion of two functional antibody Fabs. They initially modified the single Fabs site through click anchors employing an enhanced Trypsiligase variant (eTl), and this was later followed by conversion into the heterodimers through click chemistry.…”
mentioning
confidence: 99%