Immunotherapy for Ovarian Cancer: An Important Approach to Treatment

Immunotherapy for ovarian cancer stands as one of the most promising frontiers in modern cancer treatment, offering new hope for patients facing this challenging disease. 

While traditional treatments remain crucial in the fight against ovarian cancer, immunotherapy represents a paradigm shift in how medical science approaches ovarian cancer treatment by harnessing the body’s own immune system to combat cancer cells.

Understanding the Challenge

Ovarian cancer presents unique challenges in both detection and treatment. The disease often progresses significantly before diagnosis, as early ovarian cancer symptoms can mirror common digestive issues like bloating, constipation, and gastrointestinal discomfort.

Unlike some other cancers that have reliable screening methods, ovarian cancer often sneaks up on patients, making it difficult to catch in its earliest, most treatable stages.

Research shows that only about 20% of ovarian cases are detected before the cancer spreads beyond the ovaries, underlining the urgent need for more effective treatment options. This is why innovative treatments like immunotherapy have become increasingly crucial in the battle against this disease.

How Immunotherapy for Ovarian Cancer Transforms Cancer Treatment

Immunotherapy represents a fundamental shift from traditional cancer treatments. Instead of directly attacking cancer cells through surgery, radiation, or chemotherapy, immunotherapy empowers the body’s immune system to recognize and eliminate cancer cells more effectively.

The human immune system naturally possesses the ability to identify and destroy harmful cells. However, cancer cells often develop mechanisms to evade this natural defense system. Immunotherapy works by disrupting these evasion tactics and enhancing the immune system’s ability to recognize and attack cancer cells.

Ovarian Cancer Immunotherapy: Current Options

Several FDA-approved (for investigation) immunotherapy treatments are now available for ovarian cancer patients:

Checkpoint Inhibitors

Checkpoint inhibitors have become a leading immunotherapy approach. Checkpoints are natural proteins that act as regulators in the immune system, maintaining balance by preventing attacks on healthy cells while supporting T cells in fighting cancer.

However, cancer cells often exploit these checkpoint mechanisms to evade detection by the immune system. Checkpoint inhibitor drugs work by blocking specific proteins like PD-1 (Programmed Cell Death 1) and PD-L1 (Programmed Cell Death Ligand 1), effectively removing the barriers that cancer cells use to hide. This allows T cells to more effectively recognize and destroy cancer cells.

Key treatments include:

• Pembrolizumab (Keytruda): Currently being investigated in clinical trials for ovarian cancer patients, particularly those with specific genetic markers.
• Dostarlimab (Jemperli): While not specifically FDA-approved for ovarian cancer, it is approved for dMMR (DNA mismatch repair deficient) solid tumors and is being investigated in clinical trials for ovarian cancer treatment.
• Nivolumab (Opdivo): Shows promise in combination with other treatments.
• Mirvetuximab soravtansine (Elahere): FDA-approved for advanced, platinum-resistant ovarian cancer with high FR-α expression (present in approximately 80% of high-grade serous cases). This antibody-drug conjugate combines an antibody targeting the folate receptor pathway with a chemotherapy drug to deliver targeted treatment to tumors.
• TUB-040: Has received FDA fast-track designation (not full approval) as an antibody-drug conjugate targeting Napi2b, an antigen commonly overexpressed in ovarian cancer and lung adenocarcinoma.
• RC88: Another promising antibody-drug conjugate that has received FDA fast-track designation, targeting the mesothelin (MSLN) protein.

While these medications may be FDA-approved drugs for certain cancer types, they have not yet received specific FDA approval for treating ovarian cancer outside of clinical trials. Patients typically access these treatments through participation in clinical trials or case-by-case evaluations when other treatment options have been exhausted.

Monoclonal Antibodies

Bevacizumab (Avastin) represents another important category of ovarian cancer immunotherapy. This targeted antibody works by blocking the formation of new blood vessels that feed tumors (also known as angiogenesis). Cancer cells need these blood vessels to survive and grow, and they provide oxygen and nutrients that help the tumor thrive. 

By blocking a protein called VEGF (vascular endothelial growth factor), Avastin essentially helps starve the tumor of its blood supply. Clinical trials have shown this approach to be effective for both newly diagnosed patients and those whose cancer has returned after initial treatment. Additionally, Avastin is used as maintenance therapy in ovarian cancer patients for up to 22 cycles, helping to prevent or delay cancer recurrence after initial treatment.

The FDA has approved Avastin for use in combination with chemotherapy for ovarian cancer, particularly for patients with advanced disease and those experiencing recurrence.

Does Immunotherapy Work for Ovarian Cancer? The Science Behind Success Rates

The success rate of immunotherapy for ovarian cancer presents a complex picture. While immune checkpoint inhibitors (ICIs) used as single agents have shown limited response rates in clinical studies, research increasingly suggests that combining immunotherapy with other treatments may improve outcomes. 

This is why current research focuses heavily on combination approaches. Researchers have identified several factors that influence treatment effectiveness:

Tumor Microenvironment

Recent research has revealed the crucial role of the tumor microenvironment in treatment response. Think of the tumor microenvironment as the ecosystem surrounding cancer cells. It includes blood vessels, immune cells, and other supporting structures. Scientists classify tumors as either “hot” or “cold” based on their immune profile. 

“Hot” tumors contain many T-cells (immune cells that can fight cancer) that have already infiltrated the tumor tissue, particularly CD8+ T lymphocytes. They also show increased PD-L1 expression and elevated tumor mutation burden, making them more likely to respond to immunotherapy treatments. 

“Cold” tumors, while still containing T cells, primarily have regulatory T cells that suppress immune response rather than fight cancer. They lack cancer-fighting CD8+ T lymphocytes within and around the tumor. 

Additionally, cold tumors often contain tumor-associated macrophages and myeloid-derived suppressor cells, which further suppress the immune system’s ability to fight the cancer, making these tumors more resistant to immunotherapy.

This understanding has led researchers to explore ways to turn “cold” tumors “hot” by developing treatments that attract more immune cells to the tumor site.

Genetic Factors

Certain genetic markers can help predict how well a patient might respond to immunotherapy. Two important markers are: microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR). 

These markers are particularly significant because drugs like Jemperli are specifically FDA-approved for treating dMMR solid tumors. Additionally, patients with Lynch syndrome, a hereditary condition caused by mutations in mismatch repair genes, may also have dMMR tumors, making them potential candidates for this type of treatment.

Meanwhile, MSI occurs when errors in DNA replication go uncorrected. In genetic testing reports, patients commonly see results for MSH2, MLH1, and MSH6: all genes associated with Lynch syndrome. While PMS2 is also a Lynch syndrome gene, research indicates it carries a lower risk for ovarian cancer compared to the other Lynch syndrome genes.

These markers indicate that cancer cells have trouble repairing DNA damage, which can make them more visible to the immune system and, therefore, more likely to respond to immunotherapy. 

While these markers can predict better responses to immunotherapy, microsatellite instability is rare in ovarian cancer, occurring in less than 2% of cases. This low frequency highlights why researchers are working hard to find additional ways to identify which patients might benefit most from immunotherapy treatments.

Advancing Treatment Through Combinations

One of the most promising developments in ovarian cancer treatment involves combining immunotherapy with other approaches.

Recent clinical trials have shown particular success when pairing immunotherapy with PARP inhibitors, drugs that interfere with cancer cells’ ability to repair their DNA. This combination makes cancer cells more vulnerable to immune system attack and has shown particular promise in patients with BRCA mutations.

Additionally, combining immunotherapy with anti-angiogenic drugs like bevacizumab has demonstrated improved outcomes in clinical trials. 

A groundbreaking discovery from Mount Sinai researchers has revealed another promising combination: blocking interleukin-4 (IL-4) alongside immunotherapy. Their research shows that ovarian cancer cells produce IL-4 to create an immunosuppressive environment, and blocking IL-4 with existing FDA-approved eczema drugs (such as dupilumab) could potentially enhance the effectiveness of immunotherapy treatments. These combination approaches are offering new hope for patients with advanced disease, as they attack cancer through multiple pathways simultaneously.

Future Directions in Research and Clinical Progress

The field of immunotherapy continues to evolve rapidly through several promising research directions. Personalized vaccines, designed to train the immune system to recognize specific cancer cells, are showing potential in clinical trials. Some of these approaches use a patient’s own tumor cells to create customized treatments that may be more effective than one-size-fits-all solutions. 

(Learn more about how researchers are working to develop ovarian cancer vaccines.)

Adoptive cell therapy represents another innovative frontier. This approach involves modifying a patient’s own immune cells to better recognize and attack cancer cells. Early trials show encouraging results, especially when combined with other immunotherapy methods.

Researchers are also working to identify more reliable ovarian cancer biomarkers that can predict which patients will respond best to different immunotherapy approaches. This work is crucial for increasing success rates through more targeted treatment selection.

Current clinical trials explore various innovative strategies, from combined checkpoint inhibition to novel vaccine developments. These studies also investigate how to best integrate immunotherapy with conventional treatments, providing valuable insights into how ovarian cancer interacts with the immune system.

The success of immunotherapy often hinges on careful patient selection. Medical teams consider multiple factors: the cancer’s stage and type, previous treatments, overall health status, genetic markers, and the tumor’s microenvironment characteristics. This comprehensive evaluation helps determine which patients are most likely to benefit from specific immunotherapy approaches.

Shaping the Future of Ovarian Cancer Treatment

Immunotherapy represents a significant advancement in ovarian cancer treatment, offering new hope for patients who may have exhausted traditional options. While current success rates indicate room for improvement, ongoing research and clinical trials continue to expand our understanding and enhance treatment effectiveness.

As research progresses, organizations like Not These Ovaries remain committed to funding innovative research and clinical trials that advance our understanding of immunotherapy. Through continued support of novel research, particularly in understudied areas like low-grade serous ovarian cancer and borderline ovarian tumors, we move closer to more effective treatments for all women affected by this disease.