Host Institution:
İzmir Biomedicine and Genome Center (IBG)
Supervisor:
Mehmet İnan, PhD
Co-Supervisor:
Sibel Çetinel, PhD
Project Name:
Anti-PD-L1 antibody expression from the Pichia pastoris (Komagataella phaffii) as a potential immunotherapy treatment.
Project Summary:
The development of monoclonal antibodies (mABs) targeting immune checkpoints, such as programmed death-ligand 1 (PD-L1), represents a promising approach in cancer immunotheraphy. Pichia pastoris, a yeast expression host, has been used to produce recombinant proteins, including antibodies, because of its ability to produce high yields of functional proteins. It has several advantages such as faster growth rates, lower production costs, easier scalability, and the capacity for post-translational modifications. However, its native glycosylation pathways-especially O-glycosylation differ from those in human, which can influence the efficacy and pharmacokinetics of therapeutic antibodies.This study aims to employ CRISPR-Cas9 gene editing to modulate the o-glycosylation pathway in P. pastoris to enable efficient and functional expression of anti-PD-L1 monoclonal antibodies. Using precise genome editing , genes responsible for endogenous hypermannosylation will be knock out from the P. Pastoris genome and components of the human like O-glycosylation pathway will introduced or upregulated. The expected outcome is the successful secretion of anti-PD-L1 antibodies with improved folding, stability, and human compatible glycosylation profiles, retaining high binding affinity to PD-L1 targets. This strategy has the potential to establish CRIPSR-engineered P.pastoris as a cost-effective and scalable platform for therapeutics antibody production, supporting its application in cancer immunotherapy.