Sublethal Apoptotic Signaling Promotes Acquired Resistance to Immunotherapy

Novel Therapeutics & Platforms, Immunotherapies & Personalized Vaccines

Matt Hangauer, PhD (UC San Diego)

Linda Bradley PhD (SBP)

Immunotherapies have had unprecedented success in benefitting certain cancer patient populations. However, the majority of patients fail to respond to immunotherapy or develop resistance. There is little known about how cancer cells survive immunotherapy particularly during initially effective immune responses. We discovered that cancer cells can enter a dormant “persister” state to resist death signaling induced by immune cell attack and these cells seed eventual tumor recurrence. Our focus in this proposal is to understand whether these persister cells, aside from surviving, also promote immune cell exhaustion and to begin developing a therapy to target persister cells. We expect this work to advance our understanding of immunotherapy resistance and to lay the foundation for novel therapeutic approaches to help cancer patients.

“This ambitious project is intended to capitalize on our discovery of how cancer cells evade immunotherapy to begin work toward development of a novel therapy to overcome immunotherapy resistance. Curebound funding is critical to allow us to take the next steps in this high risk, high reward project as we aggressively pursue future translation of our findings to help patients.” -- Matt Hangauer