Stabilised and modular protein drugs
|Coordinator||Karolinska Institutet - Cancer Center Karolinska|
|Funding from Vinnova||SEK 2 494 400|
|Project duration||December 2016 - November 2017|
|Venture||Development and production of biologics|
Purpose and goal
The aim of this project is to develop thermostable variants of specific antibody domains and small stable antibody-like binders towards important immune-oncology drug targets. The work will be carried out by applying innovative technologies developed in the group to screen and identify protein variants with characteristics that are attractive for biologics. The work is done in close collaboration between the industrial and academic partners.
Expected results and effects
The aims have been achieved for the approved grant period. We have identified several stable antibody-like binders with phage display towards different immune-oncology target proteins. Several of these have been characterised in vitro with biophysical methods and in cell based systems with promising results where specific binding to the cell surface and activation of immune cells can be observed. Thermostable antibody domains that are lacking post translational modifications have been handed over to SOBI for further characterisation in vitro and in vivo.
Planned approach and implementation
Roughly 40000 clones from a mutant library of each antibody domain was screened for increased thermal stability with Hot-Cofi. About 30 clones with good characteristics have been identified. Preliminary melting curves has been generated with melting points from 42-66C. High affinity candidate lead drugs have been identified from our unique phage display platform towards 7 important immune oncology. All of these bind the target on cells and three of these, anti-CD73 anti-PD-L1 anti-PD-1 , has so far been shown to have activity on cells and one to have expected pharmacokinetics in mice.