Research programme 4-1
Bi-specific biologicals toolbox
Our aim is to develop a toolbox and slimmed workflow for design, generation and analysis of bi-specific biologicals to go from idea to an ability to express quantitative amounts of high quality for POC in vivo.
Bi- or multispecific biologicals are affinity proteins, traditionally based on antibody (Ab) architectures, allowing for multiple functions to be carried out by one molecule. This can be achieved through for example simultaneous targeting two or more epitopes in one target molecule, or to bring two target molecules (or cells) together, generating a biological effect not possible for a single mono-specific binder or mix of molecules. Despite the great potential of bi-specifics and more than 60 different bsAb formats developed, several bi-specific projects struggle in the transition from pre-clinical studies to the clinic due to issues concerning processability, where bottlenecks relating to product inconsistency, product aggregation, product degradation and expression levels well below normal IgG frequently are seen. It would hence be desirable to be able to screen for candidates with suitable properties earlier in the process to circumvent these issues.
Aim of WP1: Establish a panel of vectors for CHO expression of bi-specifics
Balanced expression of heavy and light chains is a key property for expression bi-specific antibodies. For bi-cistronic strategies, relative promoter strengths of the two cassettes, choice of heavy/light chain classes and fusion points affecting expression levels, secretion, and post-translational modifications, are some factors to consider. Here we explore these aspects for a selection of relevant IgG isotypes
Aim of WP2: To define a workflow for screening of the processability of bi-specifics
Fusion of novel domains to IgG can effect both expression, functional binding, ability to purify the product as well as the uniformity and stability of the product.
We will investigate and define a workflow of assays for monitoring the effect fusion points for the processability including expression level, ability to bind target, solubility and stability of product.
PI: Associate Professor Johan Rockberg
PhD student: Aman Mebrahtu
Partner companies:
