Scientists at The Wistar Institute in Philadelphia have made a groundbreaking discovery in the fight against ovarian cancer, the deadliest form of gynecological cancer.
Their innovative research, which combines immune system activation with a novel therapeutic approach, has shown significant tumor regression in preclinical lab models. Given that ovarian cancer is notoriously resistant to chemotherapy, this discovery brings renewed hope for more effective treatments in the future.
The Challenge of Treating Ovarian Cancer
Ovarian cancer remains one of the most difficult cancers to treat due to its natural resistance to chemotherapy and its ability to spread stealthily within the body. Unlike some cancers that form distinct, localized tumors, ovarian cancer often metastasizes through peritoneal fluid, which circulates in the peritoneal cavity surrounding the stomach and intestines.
A major hurdle in treating this disease is that the peritoneal cavity is inherently immunosuppressive, meaning that the body’s natural immune defenses struggle to fight tumors in this region. Because of this, standard cancer treatments, including chemotherapy and immunotherapy, often fail to generate a strong enough response to shrink tumors effectively.
Turning to a Century-Old Idea for a New Solution
To tackle this difficult-to-treat cancer, Nan Zhang, Ph.D., and his team at the Wistar Institute looked to a long-overlooked approach from the late 19th and early 20th centuries.
In the late 1800s and early 1900s, New York surgeon William B. Coley developed a technique where he injected cancer patients with dead pathogens, leading to a greater than 10% cure rate for certain cancers. Scientists later hypothesized that this effect was due to the activation of the immune system’s myeloid cells, a type of immune cell that plays a key role in fighting infections and diseases.
Building on Coley’s work, Dr. Zhang’s team sought to stimulate myeloid cells within the peritoneal cavity to mount an immune response strong enough to combat ovarian cancer.
A Novel Combination Therapy: β-Glucan and IFNγ
To achieve this immune activation, Dr. Zhang and his colleagues combined two key agents:
- Beta-glucan (β-glucan): A compound derived from pathogens that stimulates myeloid cells.
- Interferon-gamma (IFNγ): A powerful immune-signaling molecule that enhances the immune response.
By administering this dual therapy, the researchers aimed to reverse the immunosuppressive environment of the peritoneal cavity, allowing the immune system to recognize and attack ovarian cancer cells more effectively.
Breakthrough Results in Preclinical Models
The research team tested their combination therapy in preclinical models of metastatic ovarian cancer. Their findings, published in The Journal of Experimental Medicine, demonstrated that this approach significantly reduced tumor burden, even in models of ovarian cancer that had become resistant to chemotherapy.
“After treating metastatic ovarian cancer models with both β-glucan and IFNγ, total tumor burden ‘shrank substantially,’ relative to controls,” the study reported.
Even more encouragingly, the combination therapy appeared to enhance the effectiveness of chemotherapy, making tumors more receptive to traditional treatments. Given that many ovarian cancer patients experience tumor resistance to chemotherapy, this breakthrough suggests a potential new strategy for overcoming treatment resistance.
A Step Toward Future Clinical Trials
This research was funded by grants from the National Institutes of Health (NIH), and the Wistar Institute officially announced the discovery on November 21.
“Our work has opened the door to a possible new method of treating a particularly aggressive cancer,” said Brennah Murphy, Ph.D., the first author of the study.
“Ovarian cancer is infamous for resisting treatment, but we’ve shown—at the preclinical level—our treatment overcomes that resistance,” Dr. Murphy adds.
Dr. Zhang also emphasized the significance of this breakthrough, saying, “This is the first time researchers have been able to indirectly target ovarian cancer cells in peritoneal fluid by inducing an immune reaction, in preclinical models.”
The team is now focusing on advancing this research, particularly examining the role of IL27, another immune-related molecule that may further enhance their novel treatment approach.
“We look forward to taking this research further—particularly our findings on the role of IL27—so we can continue to identify other strategies to improve this new anti-ovarian-cancer approach,” Dr. Zhang added.
The Future of Immunotherapy for Ovarian Cancer
The success of this preclinical study suggests that immune system activation could become a key strategy for treating ovarian cancer, particularly in patients who do not respond well to chemotherapy. If further research, including human clinical trials, confirms the effectiveness of this approach, it could lead to a revolutionary new treatment for one of the most lethal gynecological cancers.
By drawing inspiration from century-old immune stimulation techniques and combining them with modern molecular biology, researchers at the Wistar Institute have taken an important step toward developing new hope for ovarian cancer patients worldwide.