Leveraging PROTACs to Overcome Resistance in Targeted Cancer Therapies and Immunotherapies

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Event details

Date 20.05.2022 14:0015:00  
Speaker Jin Wang, Ph.D.
Michael E. DeBakey, M.D., Professor in Pharmacology and CPRIT Scholar
Department of Pharmacology and Chemical Biology
Baylor College of Medicine
Houston, TX 77030
 
Location Online
Category Conferences - Seminars
Event Language English
Abstract
PROTACs are a novel therapeutic modality to inhibit the scaffolding functions of proteins. I will discuss our work on the first reversible covalent PROTAC targeting Bruton’s Tyrosine Kinase (BTK) (Nature Communications 2020). Serendipitously, we discovered that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and developed RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, providing a novel mechanism-of-action for PROTACs. Additionally, I will present our recent work on a novel PROTAC to boost antitumor immunities of cancer immunotherapies. One common feature for immune checkpoint blockades (ICBs), activated cytotoxic T cells, CAR-T and CAR NK cells is that they all kill cancer cells through granule exocytosis and death ligands to activate programmed cell death. However, cancer cells that are insensitive to these programed death mechanisms will evade killing mediated by the antitumor immunity. We developed a novel PROTAC that can synergize with anti-PD1 to trigger immunogenic cell death and significantly inhibit tumor growth in an immunotherapy insensitive B16F10 mouse melanoma mouse model.
 

Practical information

  • General public
  • Free

Organizer

  • Pr. Li Tang EPFL STI IBI LBI

Contact

  • Pr. Li Tang

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