Ovarian cancer remains one of the leading causes of cancer-related deaths among women. The American Cancer Society estimates that more than 20,000 women will be diagnosed with ovarian cancer in 2025. Because no reliable early-detection or screening methods currently exist, the majority of cases are diagnosed at advanced stages. While standard treatment involves extensive surgery and chemotherapy, recurrence is common, often requiring additional therapies without a realistic chance of cure. Therefore, there is an urgent need to develop new treatments that can provide patients with better outcomes.
This gap has been the focus of Stanford Cancer Institute member Oliver Dorigo, MD, PhD, the Mary Lake Polan Professor of obstetrics and gynecology (gynecologic oncology), who has been unraveling the challenges of ovarian cancer in his lab. Dorigo is the director of gynecologic oncology in the Department of Obstetrics and Gynecology. His search for more effective therapies has led to a collaboration with Stanford Cancer Institute leader Crystal Mackall, MD, founding director of the Stanford Center for Cancer Cell Therapy and the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine.
Together, they are exploring the use of chimeric antigen receptor (CAR)-T cell therapy to treat advanced ovarian cancer. This innovative immunotherapy engineers a patient’s T cells to target cancer cells when reinfused. While CAR-T therapies have achieved dramatic success in blood cancers, applying the approach to solid tumors remains challenging.
Ovarian cancer remains a very difficult disease to treat, especially when it recurs. Many patients are in dire need of better therapies.
“The goal of our CAR-T cell therapy is to achieve a high response rate with long-lasting benefit. In contrast to standard chemotherapies, cell therapies have the potential to provide durable responses,” Dorigo explained. “Ovarian cancer remains a very difficult disease to treat, especially when it recurs. Many patients are in dire need of better therapies. Working alongside Dr Mackall, a world-leading expert in cell therapy, has been a wonderful experience as we have brought the first CAR-T cell therapy to ovarian cancer patients at Stanford.”
Targeting B7-H3 in ovarian cancer
Dorigo and Mackall are focusing on B7-H3, a protein highly expressed in ovarian cancers and many other tumor types. CAR-T cells are delivered through a standard intravenous infusion or direct injection into the abdominal cavity.
“We are very excited about delivering CAR-T cells directly into the abdomen, since ovarian cancer is often confined there. This provides an outstanding opportunity for local-regional delivery,” Dorigo noted.
This collaboration—made possible by a donation from Irene and Alan Adler—led to the launch of an investigator-initiated clinical trial at Stanford, with the first patient enrolled in December 2024.
“The great advantage of an investigator-initiated trial is that Stanford controls the study procedures and owns the data. This allows us to study the clinical and biological aspects of our therapy in ways that provide the most meaningful insights. This is very different in trials managed and controlled by outside entities, including for-profit companies,” Dorigo emphasized.
Preliminary findings from the ongoing phase 1 trial are encouraging.
“In our first six treated patients, we have observed initial responses that are promising. We have also learned about side effects that have allowed us to optimize the therapy for subsequent patients,” Dorigo said. “Eventually, we plan to expand this trial to a larger cohort of patients to demonstrate meaningful clinical benefits. Our ultimate goal is to develop CAR-T cell therapy as an approved treatment option for ovarian cancer.”
Overcoming challenges in solid tumor CAR-T therapy
Despite early promise, treating solid tumors with CAR-T therapy remains difficult. Dorigo’s laboratory continues to investigate strategies to improve efficacy in mouse models of ovarian cancer, including combining CAR-T with other pharmacological agents.
“We have focused our recent work on increasing the number of T cells that are infiltrating the tumor. We are using mouse models to study different approaches that might make CAR-T cell therapy more effective,” he explained.
Exploring novel signaling pathways
Dorigo is also excited about a second clinical trial exploring a discovery made at Stanford in 2019 by Irving Weissman, MD, the Virginia & D.K. Ludwig Professor of Clinical Investigation in Cancer Research and the Stanford Cancer Institute’s founding director. Weissman’s work identified a novel “don’t eat me” signal used by cancer cells to evade macrophages—immune cells capable of digesting tumors. This signal is mediated by a protein called CD24 found on the surface of many tumor cells. CD24 interacts with a molecule on macrophages called Siglec-10, preventing the macrophages from digesting or “eating” the tumor cells. Blocking the CD24–Siglec-10 interaction with an antibody reactivates macrophages, enabling them to eliminate cancer cells. A therapeutic anti-CD24 antibody, developed by an outside company based on this Stanford invention, is now being tested in a clinical trial. On July 29, 2025, the first Stanford ovarian cancer patient was treated with this new therapy.
“It is very exciting to see this invention move from the bench to bedside so quickly. This is uniquely Stanford—bringing together top-tier scientists and providing the mechanisms to rapidly translate discoveries into clinical studies,” Dorigo said.
Looking ahead
The complexity of ovarian cancer demands persistent and multifaceted strategies. Dorigo envisions a future where more effective treatments are readily available for patients.
“Our current knowledge and molecular tools provide an unprecedented opportunity to develop therapies with improved outcomes, fewer side effects, and long-term responses,” he reflected. “We imagine that CAR-T cells will be customized based on the patients’ tumor characteristics, and therefore will offer a personalized cancer treatment. This will take time, but we are committed with amazing support from the Stanford Cancer Institute under Dr. Steven Artandi and the Stanford Cancer Cell Therapy group under Dr. Mackall’s outstanding leadership.”
