Dissecting the mechanisms of blood cancer elimination after allogeneic hematopoietic stem cell transplantation is a long-standing interest of the Warren Lab and has been a foundation for the development of techniques that harness the human immune system’s ability to eradicate cancer. The Warren Lab is focused on developing novel approaches for exploiting this ability – particularly for the treatment of patients with kidney cancer. While a large part of the team’s research is funded by government grants, philanthropic support has been, and continues to be, vital, especially in enabling them to explore new ideas and take their work in new directions like those described below.

Kidney cancer is generally considered incurable once it spreads outside the kidney. Growing evidence points toward the immune system as hope for treating and potentially curing patients with advanced kidney cancer.

Drs. Warren and Scott Tykodi and their teams are working to improve current immune-based therapeutics for kidney cancer, speed the delivery of cellular immunotherapies to the clinic, and lay the groundwork for future novel treatments. Through the following ongoing and planned collaborative research projects, they seek to learn how patients’ immune systems can rid them of their cancers and how best to extend the healing power of immunotherapy to more people with advanced kidney cancers.

Pioneering Cellular Immunotherapy for Kidney Cancer

Dr. Warren and his colleagues are developing a new cellular immunotherapy for kidney cancer aimed at a marker called 5T4. The most well-characterized marker of its kind in kidney cancer, 5T4 is found on the surface of almost all kidney cancer cells and only rarely on healthy adult cells. The team is working to genetically engineer T cells with T-cell receptors (TCRs) that recognize and attack 5T4-bearing cancer cells. They also plan to develop chimeric antigen receptors (CARs) specific for 5T4-positive kidney cancer cells. Once these promising experimental T-cell therapies have been refined and tested in the lab, the team plans to leverage Fred Hutch’s well-established expertise in cellular immunotherapy and open first-in-human clinical trials.

Improving Treatment for Kidney Cancer by Analyzing Immune Responses

The team also plans to use a revolutionary new technology, pioneered at Fred Hutch, to analyze immune system responses in patients receiving immunotherapy in order to guide patient therapy in the future or even point the way toward new immunotherapies. The high-throughput technology maps the incredible diversity of unique markers on the surface of immune cells. The team proposes to analyze how treatment with a combination of IL-2 (an immune-boosting agent) and an anti-PD-1 antibody (a molecule that helps take the brakes off the immune system) influences the specific types of T cells that infiltrate and attack the patients’ tumors. Understanding what is happening at the cellular level when patients respond well to the therapy, including which molecular markers the T cells are “seeing” on the cancer cells, could help the scientists develop personalized vaccination or even personalized cellular therapies in the future. It could also lead to a way to monitor patients’ responses to therapy and help doctors make more informed choices about treatment regimens.

Finding Genomic Signatures to Guide Personalized Immunotherapy Plans for Kidney Cancer

Under the leadership of Dr. Warren’s colleagues Drs. Min Fang and Maria Tretiakova, Fred Hutch’s treatment arm, Seattle Cancer Care Alliance, launched OncoScan last year for use in kidney cancer. OncoScan is a tumor genome–scanning technology that Dr. Warren’s team would use to determine whether the specific chromosomal abnormalities commonly found in kidney cancers are linked to patients’ outcomes after treatment with immunotherapies. If they find a link, this information could be an incredibly valuable tool for physicians and patients to use in forecasting the future after treatment — helping them choose the treatments that are most likely to offer benefit and avoid those with the lowest chance of being effective. By analyzing the genomes of patients who were treated over the past decade and whose outcomes are known, the researchers can quickly and cost-effectively get answers about disease processes that took place over a span of years.

Learn More

If you would like to know more about how you can support this innovative research, please contact Megan Little, philanthropic gift advisor at Fred Hutch, at (206) 667-5799 or mlittle2@fredhutch.org.