Immunotherapy represents a transformative approach in cancer treatment, leveraging the body’s own defense mechanisms to combat disease. It empowers the immune system to recognize and eliminate cancer cells. Ovarian cancer often presents at advanced stages and has been challenging to treat. Immunotherapy offers a promising avenue for patients facing this aggressive malignancy.
Understanding Immunotherapy for Cancer
The immune system identifies and neutralizes abnormal cells, including cancerous ones, using various immune cells like T cells. However, cancer cells can evade this detection. Some cancer cells express proteins that act as “checkpoints,” signaling immune cells to stand down.
Immunotherapy works by overcoming these evasion strategies, boosting the immune system’s ability to fight cancer. Approaches include blocking inhibitory signals, enhancing immune cell function, or introducing new immune components. This enables immune cells to recognize and eliminate tumor cells, offering a more precise and adaptable way to combat the disease. The focus shifts from directly killing tumor cells to mobilizing the patient’s own immune system, providing a dynamic and potentially long-lasting defense.
Specific Immunotherapy Treatments for Ovarian Cancer
Immunotherapy approaches for ovarian cancer aim to harness the immune system. Immune checkpoint inhibitors, such as pembrolizumab and avelumab, block proteins like PD-1/PD-L1 and CTLA-4. These proteins act as “brakes” on immune cells, which cancer cells exploit to escape detection. Blocking these checkpoints releases the “brakes” on T-cells, allowing them to attack ovarian cancer cells. While successful in other cancers, their efficacy as single agents in ovarian cancer has been modest, with response rates typically 4% to 15%. Combinations with other therapies are being investigated.
Chimeric Antigen Receptor (CAR) T-cell therapy is another immunotherapy approach. It involves collecting a patient’s T-cells, genetically modifying them to express a Chimeric Antigen Receptor (CAR), and reinfusing them. The CAR recognizes specific proteins (antigens) on cancer cells, such as mesothelin or HER2, enabling the T-cells to target and destroy ovarian cancer cells. While successful in blood cancers, its application in solid tumors like ovarian cancer is still in early-phase clinical trials, with efforts to improve effectiveness within the tumor microenvironment.
Therapeutic cancer vaccines are also being developed for ovarian cancer to educate the immune system to recognize cancer-specific targets. They use tumor-associated antigens (e.g., HER-2/neu, p53, or WT1) to train the patient’s immune cells to mount an anti-tumor response. Different types of vaccines, including cell-based (e.g., dendritic cell vaccines), peptide/protein, and genetic vaccines, are being investigated. These vaccines aim to activate tumor-specific effector cells, particularly cytotoxic T cells, to identify and eliminate ovarian cancer cells. While early studies showed limited anti-tumor efficacy, newer developments and combination strategies are yielding promising results, with some trials showing improved progression-free survival.
Other emerging approaches include oncolytic viruses, which are viruses engineered to selectively infect and destroy cancer cells while also stimulating an anti-tumor immune response. These viruses cause immunogenic cell death, releasing tumor antigens that can then prime the immune system to attack the cancer. Preclinical studies have shown significant tumor regression in ovarian cancer models using various oncolytic viruses, including adenoviruses, herpes simplex virus, and vaccinia virus. While early clinical trials have demonstrated a favorable safety profile, their impact on patient survival has been modest, leading to investigations into combining them with other immunotherapies. Adoptive cell therapies, which involve isolating and expanding a patient’s own tumor-infiltrating lymphocytes (TILs) or genetically modifying T-cells to target cancer antigens, are also being explored to enhance anti-tumor immunity in ovarian cancer.
Patient Experience and Efficacy
Eligibility for immunotherapy in ovarian cancer is not universal, as patient selection often relies on specific biomarkers found within the tumor. For example, immune checkpoint inhibitors are more likely to be effective in tumors exhibiting high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), although these characteristics are not common in ovarian cancer. PD-L1 expression, a protein found on cancer cells, is another biomarker that can indicate a greater likelihood of response to certain immunotherapies. Clear cell ovarian cancer, a specific subtype, has shown higher sensitivity to immunotherapy, and patients with this subtype who also have MSI-H may experience more favorable responses. The identification of these and other biomarkers, such as homologous recombination deficiency (HRD), helps guide treatment decisions and personalize therapy.
Immunotherapy can cause distinct side effects, known as immune-related adverse events (irAEs), which differ from those associated with chemotherapy. These adverse events occur when the activated immune system targets healthy organs and tissues, leading to inflammation. Common side effects can include flu-like symptoms, fatigue, skin rashes, itching, diarrhea, nausea, and joint pain. More serious irAEs, though less frequent, can involve inflammation of organs such as the lungs (pneumonitis), intestines (colitis), liver (hepatitis), or endocrine glands. Managing these side effects often involves corticosteroids to suppress the immune system, and prompt reporting of any new symptoms to the healthcare team is important for timely intervention.
The effectiveness of immunotherapy in ovarian cancer varies, with single-agent immune checkpoint inhibitors generally showing modest overall response rates, typically ranging from 7% to 15% in recurrent disease. However, immunotherapy can lead to durable responses in a subset of patients. Combination therapies, such as immune checkpoint inhibitors with chemotherapy, PARP inhibitors, or anti-angiogenic agents like bevacizumab, are being explored to improve outcomes, with some combinations showing increased response rates and progression-free survival in certain patient groups. Immunotherapy is often considered in later lines of treatment or as part of a combination regimen, particularly for advanced or recurrent platinum-resistant ovarian cancer. Research continues to investigate optimal combinations and identify additional biomarkers to enhance the efficacy of these treatments.