Related Experiment Video
Updated: Jan 5, 2026
11:13
A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
9.1K
An engineered ultra-high affinity Fab-Protein G pair enables a modular antibody platform with multifunctional
Tomasz Slezak1, Lucas J Bailey1, Mateusz Jaskolowski1,2
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois.
Protein Science : a Publication of the Protein Society
|October 18, 2019
Summary
Engineered antibody reagents offer versatile functionalities. A new "plug and play" platform using Fab scaffolds and protein G (GA1) enables rapid assembly of multivalent and bispecific molecules for assays and therapeutics.
Area of Science:
- Biotechnology
- Molecular Biology
- Immunology
Background:
- Engineered recombinant antibodies are replacing traditional ones in cell biology.
- Attaching functional modules to antibodies is often complex and not high-throughput.
Purpose of the Study:
- To develop a "plug and play" platform for introducing multiple functionalities into Fab-based affinity reagents.
- To demonstrate the platform's utility in proximity assays and bispecific therapeutics.
Main Methods:
- Developed a platform exploiting the interaction between Fab scaffolds (FabS) and a protein G domain (GA1).
- Genetically engineered GA1 to link Fab modules, creating multivalent and bispecific constructs.
- Applied the platform to a β-lactamase (BL) split enzyme proximity assay and a Bi-specific T-cell engager (BiTE) model.
Main Results:
- Successfully created a versatile Fab-GA1 platform for modular reagent assembly.
- Demonstrated the platform's application in a BL split enzyme detection assay.
- Engineered potent BiTE-like molecules with interchangeable Fabs for targeted cancer cell killing.
Conclusions:
- The Fab-GA1 platform offers a facile method for creating diverse antibody-based reagents.
- This modular approach facilitates rapid engineering of reagents for diagnostics and therapeutics, including BiTEs.
- The "plug and play" nature allows for easy interchangeability of targeting Fabs for different cancer types.
Related Concept Videos
01:10Antibody Structure
65.1K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.1K
01:57Protein Complexes with Interchangeable Parts
2.8K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.8K