Annually, around 300,000 individuals worldwide receive a diagnosis of ovarian cancer, leading to approximately 180,000 deaths. Despite advancements in surgery and chemotherapy, ovarian cancer remains a highly deadly form of cancer. Therefore, there is a need for new and innovative treatment methods to enhance the outcomes for patients. Immunotherapy, a proven effective approach in various cancers, is already being utilized in clinical practice.
This review discusses essential strategies in using immunotherapy for ovarian cancer, summarizing findings from clinical studies that explore promising immunological avenues for future treatment improvements. Current noteworthy strategies include using checkpoint blockade agents, vaccines, adoptive cell transfer, and combinations of these methods.
Although these approaches show promise, it is crucial to conduct large, controlled, and randomized studies to validate their effectiveness before incorporating them into standard clinical practice.
What is Ovarian Cancer?
Ovarian cancer originates in the female reproductive organs responsible for egg production—the ovaries. Detecting ovarian cancer early poses a challenge, often remaining unnoticed until it spreads in the pelvic and abdominal regions. In advanced stages, treatment becomes more challenging, and the prognosis may be grave.
The initial phases of ovarian cancer typically manifest without noticeable symptoms. As the disease progresses, symptoms emerge, yet they tend to be non-specific, including indicators like a decrease in appetite and weight loss.
Types of Ovarian Cancer
Ovarian cancer encompasses various types, each classified based on the specific cells from which they originate. The primary types of ovarian cancer include:
Epithelial Ovarian Cancer (EOC)
- Serous Carcinoma: The most common type, characterized by cells that line the ovary surface.
- Mucinous Carcinoma: Arises from mucous-producing cells in the ovary.
- Endometrioid Carcinoma: Resembles cells of the uterine lining and is often associated with endometriosis.
- Clear Cell Carcinoma: Characterized by clear-appearing cells and tends to have a poorer prognosis.
Stromal Ovarian Cancer
- Granulosa Cell Tumors: Originating in the cells that support the egg development, these tumors often produce estrogen.
- Sertoli-Leydig Cell Tumors: Rare tumors that may produce male hormones.
Germ Cell Ovarian Cancer
- Dysgerminoma: A rare and usually malignant tumor composed of germ cells.
- Endodermal Sinus Tumor (Yolk Sac Tumor): Common in young women, often aggressive.
- Teratoma: Contains multiple types of tissues, including hair, teeth, and bone.
Mixed Epithelial and Stromal Tumors
- Tumors that have characteristics of both epithelial and stromal cells.
Each type of ovarian cancer may have different characteristics, risk factors, and treatment approaches. The specific subtype is identified through pathological examination after surgery or biopsy, guiding the development of a tailored treatment plan for the individual patient.
What is Immunotherapy?
Our immune system serves as a defender against viruses, bacteria, and various infections. Ideally, it would also protect us from cancer cells, but unlike foreign invaders, cancer cells are part of our own body. Consequently, the immune system often struggles to recognize and combat cancer effectively.
Immunotherapy emerges as a groundbreaking cancer treatment, aiming to educate the immune system on identifying and responding to cancer cells.
Immunotherapy encompasses diverse approaches, including:
Immune Checkpoint Inhibitors: Medications assisting the immune system in better detecting cancer cells.
Monoclonal Antibodies: Manufactured antibodies designed to target specific aspects of cancer cells.
Chimeric Antigen Receptor T-Cell Therapy (CAR T-Cell Therapy): Training specific immune cells, called T cells, to locate and eliminate cancer cells.
Cytokines: Proteins that stimulate the immune system.
Immunomodulators: Medications that enhance the immune system’s activity.
Cancer Vaccines: Vaccines triggering the immune system to respond to cancer.
Oncolytic Viruses: Modified viruses engineered to infect and destroy cancer cells.
Immunotherapy represents a multifaceted approach empowering the immune system to recognize and combat cancer, providing hope for more effective and personalized cancer treatments.
Immunotherapy for Ovarian Cancer
Immunotherapy remains a relatively uncommon avenue for treating ovarian cancer, as indicated by a 2020 review of studies. Most forms of immunotherapy for ovarian cancer are currently in the experimental stage, undergoing testing in clinical trials. However, for individuals facing advanced ovarian cancer, there is a potential option through immunotherapy, though access may involve participation in a clinical trial facilitated by the attending physician.
Notably, the immune checkpoint inhibitor pembrolizumab has been identified by the American Cancer Society as a potential immunotherapeutic intervention for specific scenarios in ovarian cancer. This includes cases of advanced ovarian cancer, instances where the cancer exhibits particular genetic changes or levels, and situations where the cancer resumes growth after prior treatments like chemotherapy or targeted therapy. Pembrolizumab is administered through intravenous (IV) infusion, with the recommended frequency being every 3 weeks or every 6 weeks, as specified in the drug label.
While immunotherapy presents a promising avenue for certain ovarian cancer conditions, its application remains contingent on the outcomes of ongoing clinical trials, and enrollment in such trials may be necessary for those considering this treatment option. As research advances, the role of immunotherapy in ovarian cancer treatment continues to be explored, offering hope for improved therapeutic approaches.
Immunotherapy and Combination Therapy
To enhance the effectiveness of immune checkpoint inhibitors (ICIs) in treating ovarian cancer, researchers are exploring combination therapies, especially with chemotherapy and other cancer drugs. Early trials, like one in 2020 involving 40 individuals with recurrent ovarian cancer, tested a combination of pembrolizumab, a targeted therapy drug, and a chemotherapy drug. Encouragingly, 95% of participants experienced some benefit from this combined treatment, with about a quarter enjoying a response lasting over 12 months.
Another approach involves using different combinations of ICIs. A separate 2020 trial discovered that combining ipilimumab with some other immunotherapy drug not only improved the treatment response rate but also slightly extended the time before the cancer progressed. These findings indicate promising avenues for more effective and prolonged ovarian cancer treatment by combining immune therapies with other drugs.
Who Gets Immunotherapy for Ovarian Cancer?
For ovarian cancer, surgery and chemotherapy are usually the first treatments. But if the cancer comes back later on, there’s now another option called immunotherapy. It doesn’t work for everyone, but it’s becoming more common for people with recurring ovarian cancer.
Doctors are finding that combining immunotherapy with other treatments can improve overall health outcomes. This includes using it alongside chemotherapy and radiation therapy, which kill cancer cells. It can also be paired with drugs that stop the growth of blood vessels feeding tumors and inhibitors that prevent cancer cells from fixing damaged DNA. By bringing together these different treatments, doctors aim to create a well-rounded approach to tackle recurring ovarian cancer and enhance the chances of a positive outcome.
Immune Checkpoint Inhibitors For Ovarian Cancer
Immune checkpoint inhibitors represent a groundbreaking approach in the realm of ovarian cancer treatment, leveraging the intricate mechanisms of the immune system to combat malignancies. An integral facet of the immune system is its ability to discern between normal and abnormal cells, ensuring that the body’s defense mechanisms do not inadvertently attack healthy tissues.
This discrimination is orchestrated through the utilization of “checkpoints” – proteins found on immune cells that regulate the initiation or suppression of immune responses. Cancer cells, however, can exploit these checkpoints to evade immune system detection and subsequent destruction. Enter immune checkpoint inhibitors, a class of drugs designed to disrupt this evasion strategy employed by cancer cells.
Pembrolizumab stands out as a notable immune checkpoint inhibitor specifically targeting the PD-1 protein on certain immune cells, known as T cells. PD-1 normally functions to prevent these cells from launching attacks on other cells within the body. By obstructing PD-1, drugs like Pembrolizumab enhance the immune response directed against cancer cells. The outcome of this intervention can manifest as the shrinkage of tumors or a deceleration in their growth.
This innovative immunotherapeutic approach finds applicability in individuals with advanced ovarian cancer characterized by specific genetic features. Pembrolizumab is particularly effective in cases where there are high levels of microsatellite instability (MSI) or alterations in the mismatch repair (MMR) genes. Importantly, this treatment is reserved for instances where ovarian cancer exhibits resurgent growth following prior rounds of chemotherapy or other drug regimens.
Administered through intravenous (IV) infusions at three-week intervals, Pembrolizumab exemplifies the strides made in precision medicine, offering renewed hope and therapeutic avenues for individuals facing the complexities of advanced ovarian cancer. Through the modulation of immune checkpoints, this innovative therapy reinvigorates the body’s defenses, marking a significant advancement in the ongoing battle against this formidable disease.
What are PARP Inhibitors?
PARP inhibitors represent a targeted therapy within the realm of cancer treatment, specifically designed to identify and disrupt the functioning of cancer cells. This form of treatment aims to minimize harm to healthy cells while effectively impeding the progression of the disease. Notably, when paired with immunotherapy, PARP inhibitors have shown considerable promise in enhancing outcomes for ovarian cancer patients. Among the commonly used PARP inhibitors are niraparib (Zejula) and Olaprib, both demonstrating efficacy, with niraparib approved by the FDA as a once-daily pill for ovarian and fallopian tube cancer.
In the context of ovarian cancer, PARP inhibitors are considered a significant advancement, offering a potential means to slow disease progression and extend the duration between remission and recurrence. Often referred to as ovarian maintenance treatment, these inhibitors play a crucial role in addressing the challenge of recurrent disease, a concern faced by over 80% of ovarian cancer patients after achieving initial remission.
The advent of PARP inhibitors heralds a new era in cancer therapeutics, providing hope for improved outcomes and prolonged periods of disease control, particularly in the challenging landscape of ovarian cancer management. The combination of targeted PARP inhibition and immunotherapy reflects a promising avenue in the ongoing quest for more effective and tailored cancer treatments.
Immunotherapeutic Medications Used in Ovarian Cancer Treatment
Immunotherapy is emerging as a promising avenue in the treatment of ovarian cancer, although its definitive role is still under exploration. Presently, there are three immunotherapy drugs approved by the FDA for ovarian cancer, and ongoing research holds promise for additional options.
Pembrolizumab
Pembrolizumab is an immunomodulator classified as a checkpoint inhibitor. This drug modifies the immune system’s behavior to enhance the recognition of cancer cells by immune cells. Typically administered intravenously every three weeks, Pembrolizumab shows efficacy in ovarian cancer treatment.
Dostarlimab
Dostarlimab, another immunomodulator functioning as a checkpoint inhibitor, was initially designed for endometrial cancer treatment. It has gained FDA approval for specific advanced-stage tumors located in the ovaries, colon, and other body regions.
Additional immunotherapy drugs under investigation for ovarian cancer treatment include Durvalumab and Avelumab. These medications signify a dynamic landscape of research and potential advancements in diversifying treatment options for ovarian cancer patients.
DENVAX: Dendritic Cell Therapy For Ovarian Cancer
Dendritic cell therapy is an innovative approach being explored for the treatment of ovarian cancer. In this method, dendritic cells, which play a crucial role in the immune system by presenting antigens to other immune cells, are harvested from the patient. These dendritic cells are then modified or loaded with antigens specific to ovarian cancer cells in a laboratory setting.
Once modified, these enhanced dendritic cells are reintroduced into the patient’s body. The goal is to stimulate a more robust immune response against ovarian cancer. By presenting cancer-specific antigens, dendritic cells essentially educate the immune system to recognize and target the cancer cells, enhancing the body’s natural defense mechanisms.
Early research and clinical trials suggest that dendritic cell therapy holds promise as a personalized and targeted treatment option for ovarian cancer. As the field of immunotherapy continues to advance, dendritic cell therapy stands out as a potential avenue for improving outcomes and offering new hope for individuals grappling with ovarian cancer.
While immune checkpoint inhibitors have shown limited effectiveness in treating ovarian cancer patients, there’s promising potential in utilizing dendritic cell vaccines to boost T-cell responses. Research suggests that stimulating T-cell responses is crucial for achieving positive outcomes with immune checkpoint inhibitors in ovarian cancer patients. By enhancing T-cell responses through dendritic cell vaccines, there is an optimistic outlook for improving clinical responses to immune checkpoint inhibitors in the context of ovarian cancer.
Incorporating this information seamlessly, it’s essential to underscore that the integration of dendritic cell therapy holds the key to enhancing the efficacy of immune checkpoint inhibitors in ovarian cancer treatment. This strategic approach aligns with the evolving landscape of immunotherapy, showcasing a potential avenue for optimizing treatment outcomes in this patient population.
Potential Side-Effects of Immunotherapy
Immunotherapy, while a valuable treatment avenue for certain cancer types, may induce various side effects that warrant consideration. These potential side effects encompass a spectrum of manifestations, including:
Fatigue: Individuals undergoing immunotherapy may experience a sense of weariness.
Skin Issues: A skin rash or itching may manifest as a reaction to immunotherapy.
Gastrointestinal Disturbances: Diarrhea or other gastrointestinal problems may arise as side effects.
Digestive System Discomfort: Nausea, vomiting, and loss of appetite are among the potential digestive system-related side effects.
Respiratory Challenges: Shortness of breath and coughing may occur in some cases.
Neurological Symptoms: Headaches, muscle, or joint pain may be observed.
General Discomfort: Fever might be experienced by individuals undergoing immunotherapy.
While these side effects are common, it’s crucial to acknowledge that more severe reactions are possible, including:
Allergic Reactions: Some individuals may experience severe allergic reactions to immunotherapy.
Respiratory Complications: Lung problems may emerge as a more serious side effect.
Liver Inflammation: Immunotherapy could lead to inflammation of the liver.
Intestinal Challenges: Serious intestinal issues may occur in certain cases.
Endocrine System Impact: Problems with hormone-producing glands are a potential concern.
Renal Issues: Kidney problems may be observed as rare but severe side effects.
It’s imperative to highlight that not everyone undergoing immunotherapy will encounter side effects, and some may only experience mild, self-resolving manifestations. Nonetheless, healthcare professionals should maintain vigilant monitoring to promptly identify and address any potential side effects in individuals undergoing immunotherapy.
Final Note
Immunotherapy is emerging as a hopeful treatment for ovarian cancer, with clinical trials displaying encouraging results. It appears to extend progression-free survival and shrink tumors in some cases. As healthcare decisions are individualized, consulting with a healthcare professional is key for personalized treatment guidance tailored to each patient’s unique needs and responses.
