High-throughput platform helps engineer fast-acting covalent protein drugs
Why it matters: This platform enables the development of next-generation biologics like IB101 and IB201, improving cancer and cytokine therapies.
- Bobo Dang and Ting Zhou's team at Westlake University/Westlake Laboratory developed a high-throughput platform for engineering fast-acting covalent protein therapeutics.
- The platform combines yeast surface display with chemoselective protein modification to screen diverse crosslinkers and millions of protein variants, optimizing warhead placement for rapid and irreversible target engagement.
- IB101, a covalent PD-L1 antagonist developed using this platform, demonstrated strong antitumor activity in mouse models and achieved durable target engagement despite a short in vivo half-life, outperforming conventional antibody-based therapies.
- IB201, an engineered covalent IL-18 variant, rapidly forms a covalent interaction with its receptor, enhancing signaling strength and duration, and showed potent antitumor immune responses without systemic toxicity in vivo.
Scientists at Westlake University/Westlake Laboratory have developed a high-throughput platform that addresses the kinetic challenge in covalent protein drug development, enabling the creation of fast-acting therapeutics like IB101 for PD-L1 and IB201 for IL-18. This innovative system, detailed in Science, overcomes the rapid in vivo clearance of miniproteins by optimizing warhead placement for accelerated covalent bond formation, paving the way for next-generation biologics with enhanced efficacy and safety.
