Investigating PROTAC-mediated antigen degradation as a novel strategy to enhance cytotoxic T-cell responses against cancer in vivo

Project summary

Recent developments in reprogramming the patient´s immune system to destroy tumors have revolutionized cancer treatments, but often remain ineffective due to immune evasion strategies that allow cancer cells to escape from the radar of immunity. While current therapies aim to enhance the number and activity of tumor‐specific immune cells, there is currently no available strategy that improves tumor visibility to enhance recognition by the immune system. To address this unmet clinical need, Dr. Schliehe´s team will investigate bispecific molecules – so called proteolysis-targeting chimeras (PROTACs) – as novel immunotherapeutic tools to increase the “immune visibility” of cancer cells and thereby facilitate their immune‐mediated killing.

The project will impact the field of cancer immunotherapy by providing first in vivo evidence that PROTACs can be used as novel tools to enhance MHC class I‐mediated CTL responses in cancer. It therefore extends previous discoveries in the PROTAC field towards new directions and applications and provides the rationale to design PROTACs directly targeting endogenous cancer antigens, permitting the clinical translation of this novel approach.