Improving Immune Checkpoint Therapy for Cancer

What biomedical issue did you address in your research, and what did your studies find?

My research project aimed to improve outcomes for patients with cancer who are unable to respond to current treatments. My work focused on immune checkpoint therapies, specifically therapeutics that target a protein known as PD-L1. The protein is known to engage with its receptor on T cells, suppressing T cells' ability to effectively kill tumors.

Although many cancers express PD-L1, many patients do not respond to therapies that target this protein.

Our team found that even when therapies interfere with PD-L1, the protein can "recycle" itself and return to the cell surface. We also found that, even though tumor cells express PD-L1, cancer-fighting immune cells known as myeloid cells also express this protein. To fully remove the protein, my lab developed a new antibody, called H1A, that degrades PD-L1 and prevents the recycling process.

Our studies found that H1A removes PD-L1 from myeloid cells, which boosts their ability to fully activate T cells, thereby improving the killing of tumor cells. Our approach is now being developed as a clinical trial at Mayo Clinic, providing promise and hope for patients.

What motivates you?

My motivation for studying cancer immunology stems from my own family history of cancer. A close family member was diagnosed with early-stage colon cancer and was able to overcome it thanks to modern medicine. However, I have other relatives who were not so lucky. The goal of developing new therapies that can further aid cancer patients is a huge driving force for me.

Mayo Clinic Graduate School of Biomedical Sciences has provided me with a community that fosters collaboration across groups. Additionally, I have had access to a great number of resources that have allowed me to fully dissect a research question in a highly translatable way. I've learned that the path to discovery can lead in a completely unanticipated direction!

A guiding motto for me is a quote from Nobel Prize-winning biochemist Albert Szent-Gyorgyi: "A discovery is said to be an accident meeting a prepared mind." I'm also motivated by the guidance of my mentor, Haidong Dong, M.D., Ph.D., who reminds students, "Don't be discouraged, and always follow your data."