Ovarian cancer is a challenging disease, often diagnosed at advanced stages, which historically leads to lower survival rates despite conventional treatments like surgery and chemotherapy. The need for more effective therapies is evident, as many patients experience disease recurrence. Immunotherapy has emerged as a promising approach in cancer treatment, working by harnessing the body’s own immune system to target and fight cancer cells. This innovative strategy is now being explored for its potential to improve outcomes in ovarian cancer.
How Immunotherapy Works
The immune system normally functions as the body’s defense mechanism, constantly patrolling for and eliminating abnormal cells, including those that could become cancerous. This process, known as immune surveillance, helps prevent tumor growth and spread. However, cancer cells can develop sophisticated strategies to evade detection and destruction by the immune system, such as creating an immunosuppressive environment around the tumor.
Immunotherapy re-enables or enhances the immune system’s natural ability to detect and destroy abnormal cells. Instead of directly attacking cancer cells, these drugs empower the patient’s own immune cells to recognize and eliminate tumors. This can involve training the immune system to better identify cancer cells or helping the body produce more cancer-fighting immune cells. By modifying the immune system, immunotherapy aims to overcome cancer cells’ evasion tactics, allowing the immune response to effectively target the malignancy.
Why Immunotherapy for Ovarian Cancer
Ovarian cancer presents particular challenges with traditional treatments, as many patients experience recurrence and develop resistance to chemotherapy. The unique characteristics of ovarian tumors suggest they might be responsive to immune-based therapies, offering a new avenue for treatment. For instance, the presence of immune cells infiltrating ovarian tumors, known as tumor-infiltrating lymphocytes (TILs), has been linked to improved patient survival.
The tumor microenvironment in ovarian cancer is often immunosuppressive, containing factors and cells that hinder the immune system’s anti-tumor function. This environment can be rich in immune-suppressive molecules that promote tumor growth and inhibit immune cell activity. Certain genetic mutations common in ovarian cancer can also lead to an increased number of neoantigens, potentially making the cancer more “visible” to the immune system. These factors provide a scientific basis for exploring immunotherapy as a therapeutic option for ovarian cancer.
Key Immunotherapy Approaches for Ovarian Cancer
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are a class of immunotherapy drugs that block specific proteins, or “checkpoints,” on immune cells or cancer cells. Cancer cells exploit these checkpoints, like PD-1 and PD-L1, to “turn off” immune responses and evade destruction. By blocking this interaction, these inhibitors effectively “release the brakes” on the immune system, allowing T cells to recognize and attack cancer cells more effectively. Another target is CTLA-4, which also negatively regulates T-cell function. Blocking CTLA-4 can enhance T-cell activation, reducing the immunosuppressive tumor microenvironment.
PARP Inhibitors and Immunotherapy Combination
Combining PARP inhibitors with immunotherapy is an area of research for ovarian cancer. PARP inhibitors disrupt proteins cancer cells use to repair their DNA, leading to DNA damage. This DNA damage can increase neoantigens (new antigens) and the tumor mutational burden, making the cancer more immunogenic and susceptible to immune checkpoint inhibitors. Preclinical studies show PARP inhibition can alter the tumor microenvironment to become more receptive to immunotherapy. Clinical trials are exploring these combinations, with some showing antitumor activity and a tolerable safety profile in recurrent ovarian carcinoma.
Other Emerging Therapies
Beyond checkpoint inhibitors and PARP inhibitor combinations, other immunotherapy approaches are being investigated for ovarian cancer. Adoptive cell therapies, such as CAR T-cell therapy, involve taking a patient’s own T cells, genetically modifying them to recognize specific cancer proteins, and then reintroducing them to attack cancer cells. While CAR T-cell therapy has shown success in blood cancers, its application in solid tumors like ovarian cancer faces challenges due to the immunosuppressive tumor microenvironment and tumor heterogeneity. Ongoing research explores ways to enhance their effectiveness, such as targeting multiple antigens or administering them directly into the tumor area.
Cancer vaccines are another area of research, aiming to train the immune system to recognize and attack cancer cells by presenting specific tumor proteins. These vaccines can be personalized and have led to disease control in some patients with advanced, drug-resistant ovarian cancer when combined with other therapies.
Current Status and Patient Experience
Immunotherapy for ovarian cancer is used in specific contexts, such as recurrent disease or in patients with certain genetic profiles. Response rates to single-agent immune checkpoint inhibitors have been modest. This has led to a strong focus on combination therapies to improve efficacy.
Patients undergoing immunotherapy may experience side effects, known as immune-related adverse events, due to the immune system attacking healthy tissues. Common side effects include fatigue, cough, nausea, skin rash, and diarrhea. More serious, though less frequent, side effects can affect various organs. Patient eligibility often involves biomarker testing, though the predictive value of these markers is still being refined. Ongoing research continues to explore new combinations and identify better biomarkers to personalize treatment and improve outcomes for women with ovarian cancer.