SHM-XEL™ Platform
Overview
The SHM-XEL™ platform is an in vitro antibody discovery and optimization platform that couples somatic hypermutation with mammalian cell display in full-length or fragment formats. Desired antibody properties are evolved by co-expression of activation induced cytidine deaminase (AID) with antibody heavy and light chains in mammalian cells where the intact antibody is simultaneously displayed on the cell surface and secreted into the growth medium. Selection of antibodies with optimal properties is achieved using high-throughput screening methodologies. This versatile platform can be used for both discovery of new antibodies and optimization of existing antibodies to generate candidates with desired binding and specificity properties for therapeutic applications.
Features
- Reproduces the natural mechanism of antibody maturation and maintains native patterns of amino acid changes to improve antibody binding properties without in vivo limitations and biases
- Antibody heavy and light chains are co-evolved simultaneously and selected in their intended final format (e.g., full-length, fragment)
- Mutations of functional significance are generated across the entire variable region
- Uses Deciduous™ and APEX™ expression formats, AnaptysBio’s proprietary leading-edge mammalian cell expression, secretion and surface display technologies
- Uses high-throughput multi-parameter flow cytometry technology to select for desired antibody properties such as higher affinity, cross-reactivity, expression and stability
- Uses the ABELmAb™ series of proprietary fully human antibody libraries for de novo discovery and optimization applications
Applications
- Antibody Optimization (e.g., to improve binding affinity, cross-reactivity, expression and stability)
- Antibody Humanization
- Antibody Discovery
The SHM-XEL™ platform’s unique versatility, with its unprecedented range of starting points and applications, provides project teams the ability to optimally tailor activities based on the project’s objectives and availability of starting materials.
Somatic Hypermutation (SHM)
Central to AnaptysBio’s SHM-XEL™ platform is SHM, a natural process that occurs in a specific cell type of the immune system (B-cells) during the selection and maturation of antibodies. This process is the means by which the body generates potent antibodies to fight disease.
SHM is a controlled process of introducing variability into the binding region of an antibody gene sequence and is catalyzed by the B-cell specific enzyme, Activation-Induced Cytidine Deaminase (AID). Antibody genes have evolved to be naturally templated to attract AID to the binding region. In the binding region, AID recognizes signature DNA motifs and initiates the process of SHM by deaminating a specific DNA residue (deoxycytidine) resulting in a different residue (deoxyuridine) that is not normally found in DNA. This change is recognized as a mistake by the cell, which attempts to correct the mistake by introducing additional DNA sequence modifications. This process of SHM results in non-random changes being introduced at functionally significant positions in the binding region sequence of the antibody. As a result, a large diversity of antibodies with different binding properties is created. The best antibodies for binding to a particular disease target are then selected by the body and produced in larger quantities to create a uniform army of antibodies well suited for fighting the disease.
The pioneering work of AnaptysBio’s founding scientific advisors was fundamental to elucidating the mechanism and role of AID in SHM, and the SHM-XEL™ platform is based on their insights.
Following a process known as recombination, B cells generate a large number of antibodies with different binding characteristics. Through subsequent SHM, an even greater, more potent and diverse assortment of antibodies is created. Only those B cells expressing antibodies with stronger binding to the disease target survive and go on to generate large quantities of therapeutically useful antibodies.