The evolution of cancer immunotherapy: Dr. Urba shares his insights
June is Cancer Immunotherapy Month, a time to celebrate the significant strides made in cancer care through groundbreaking immunotherapy research.
Since 1993, Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, has been a pioneer in this critical field. Under the leadership of Walter J. Urba, M.D., Ph.D., chief medical officer, Providence Cancer Institute, and director of cancer research, Earle A. Chiles Research Institute, dedicated physicians and scientists work together to integrate lab research and clinical trials with patient care. Earle A. Chiles Research Institute stands as a center of excellence for precision immuno-oncology and cellular therapy.
We recently caught up with Dr. Urba to talk about the evolution of immunotherapy in the past three decades and to learn about his vision for its future.
Cancer immunotherapy explained
Cancer immunotherapy is a specialized field focused on empowering the immune system to work harder and smarter to identify and destroy invading cancer cells. This innovative approach works by:
- Boosting and improving the immune response
- Targeting cancer cells
- Identifying mutations through genomics to target cancer cells
- Marking cancer cells
- Antibody delivers toxic payloads (drugs or radioactivity) directly to tumor cells
Compared to traditional treatments like chemotherapy, radiation therapy and surgery, immunotherapy is a more personalized approach and potentially less harmful to healthy cells.
“When we began our research here 30 years ago, immunotherapy was new. The idea had been around for more than 100 years, but no one could figure out how to get it to work in patients,” says Dr. Urba.
But clinical trials finally demonstrated its potential, sparking a revolution in cancer treatment. When Dr. Urba joined Providence, the vision was to build a cancer program grounded in immunotherapy.
Today, immunotherapy is part of the standard of care for many types of cancer and remains a vibrant area of research worldwide. “It’s been a big advance in cancer treatment, but there’s still plenty of opportunity to make it better,” says Dr. Urba.
Immunotherapy evolves
In less than 20 years, immunotherapy, particularly through the efficacy of checkpoint inhibitors, has become a mainstream treatment and is recognized as the fourth pillar of cancer care, alongside chemotherapy, surgery and radiation therapy. Checkpoint inhibitors “turn off the brakes” of the immune system allowing T cells to expand and destroy cancer cells. Checkpoint inhibitor therapy has been shown to successfully combat solid tumor cancers, such as melanoma, lung, breast and head and neck cancers.
Dr. Urba was the principal investigator on the global clinical trial for ipilimumab, the first checkpoint inhibitor to receive approval as a cancer treatment from the Food and Drug Administration (FDA). He also was senior author of the first scientific paper that showed that this approach improved survival of patients with melanoma. Brendan Curti, M.D., Robert W. Franz Endowed Chair for Clinical Research, was co-investigator on the study.
Building on this success, Providence researchers have explored a wide array of immunotherapy strategies, driven by promising results from laboratory work and clinical trials.
Dr. Urba highlights four key research areas at Earle A. Chiles Research Institute that demonstrate the speed and breadth at which immunotherapy is evolving and opportunities for the future:
- Combination therapy: Combining two or more treatments to enhance the immune system. Studies evaluate the combination and sequence of therapies, which may include chemotherapy, radiation or surgery. The NIRT study, initiated at Earle A. Chiles Research Institute, showed the benefits of combining immunotherapy and radiation therapy prior to surgery.
- Cellular therapy: Developing anti-tumor immune cells in the lab to be reintroduced to patients to create a more effective immune response. Providence Cancer Institute offers advanced cellular therapies such as CAR T-cell therapy, tumor infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2). In 2022, the New England Journal of Medicine published an autologous T-cell transfer therapy study initiated at Earle A. Chiles Research Institute that successfully treated a patient with metastatic pancreatic cancer. And recently, the FDA approved an autologous adoptive cell transfer therapy for people with melanoma based on the results of a clinical trial enrolling patients at Providence Cancer Institute. These studies represent significant milestones for Providence researchers and the field of immuno-oncology.
- Antibody-based therapy: Antibodies were the first approved immunotherapies.
Currently, antibodies are being tested as vehicles to deliver drugs or radioactive molecules directly to tumor cells. Specially designed antibodies (bi-specific antibodies) can deliver T cells to kill cancer cells. This is a promising and quickly evolving field of study that can improve treatment and minimize side effects. Antibody-based research was a major topic at the 2024 ASCO Annual Meeting in early June, and some of our researchers participated in related studies presented there. - Cancer vaccines: Leveraging mRNA technology to treat cancer.
These are targeted therapies that can be given alone or in combination with other therapies. Vaccines enhance the response of the immune system and can be personalized, which may mean better antitumor results and fewer side effects. There are several studies underway at Earle A. Chiles Research Institute that are evaluating vaccines for solid tumor cancers, including uveal melanoma, breast and head and neck cancers.
Looking ahead: Genomics and immunotherapy
Immunotherapy research often intersects with genomics, which enables researchers to identify changes in a cancer cell caused by a virus or mutations to the DNA. Providence Molecular Genomics Laboratory uses next generation sequencing to simultaneously test many genomic biomarkers from tissue and blood samples in a matter of days. The information provides a molecular profile to help oncologists recommend a targeted therapy or immunotherapy treatment for cancer patients.
“Genomics and immunotherapy go hand-in-hand,” says Dr. Urba. “If we can understand the tumor and the immune system’s response better at the time of diagnosis, we can then predict what combination of drugs will give them the best chance of cure,” says Dr. Urba. “I think the work at Earle A. Chiles Research Institute is an example of where genomics and immunotherapy have come together to improve therapy for patients with cancer.”
Attracting immunotherapy experts
Attracting talented physicians and scientists is crucial to staying at the forefront of cancer immunotherapy research. It is equally important that the team have a diverse range of interests and expertise in cancer types, and an interest in the role of the immune system in cancer therapy. Our women researchers play a significant role in scientific advancement, contributing invaluable insights and driving innovation in the field.
Recently, Jianguo Huang, Ph.D., Terry Medler, Ph.D., and Di Wen, Ph.D., joined Earle A. Chiles Research Institute, adding to the depth of our renowned team of researchers.
One way Providence Cancer Institute and Earle A. Chiles Research Institute helps train professionals in the field is through the Immuno-Oncology Research Fellowship. The one-year program offers physicians subspecialty training in immunology, immunotherapy and translational clinical trials.
“It’s important to be able to train physicians how best to care for patients receiving these therapies,” says Dr. Urba. “And we also want to prepare professionals for continued scientific investigations. There’s plenty of work to be done in this field, so it’s important to know we are training the people who can solve the problems we have left unsolved.”
Patient-focused care
Central to the mission of immuno-oncology research are the patients. Dr. Urba and his team are driven by a commitment to patient-first care, and passionate about helping individuals live healthier, happier lives.
“Seeing someone whose x-rays are clear, whose life returns to normal is gratifying. And then to see them come back year after year as grateful patients, that keeps me going.”
The compassionate and skilled researchers and physicians at Providence embody the hope and determination essential to conquering cancer. “If we just hang in there and keep at it, we're going to figure this out,” says Dr. Urba.
