Immunotherapy For Ovarian Cancer

  • Isla Cogle BSc Immunology student, University of Glasgow
  • Pranjal Ajit Yeole Bachelor's of Biological Sciences, Biology/Biological Sciences, General, University of Warwick, UK

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Most people are familiar with the terms chemotherapy and radiotherapy when it comes to cancer therapy- these have long been the go-to strategies. However, a cutting-edge approach called immunotherapy is currently being developed and perfected. This harnesses the body’s natural defences to fight the disease and promises fresh hope and novel strategies in the fight against ovarian cancer. 

Overview of ovarian cancer 

Ovarian cancer develops when cells in the ovaries or the surrounding areas mutate, which causes them to grow and divide uncontrollably, resulting in a mass of cells called a tumour. The cells can survive in toxic conditions that normal body cells cannot. They may also metastasise, meaning some cells separate from the initial tumour, spreading throughout the body. Ovarian cancer most commonly spreads to the liver, fluid around the lungs, other areas in the abdomen such as the intestines or bowel, and lymph nodes.1

Ovarian cancers are challenging to treat and are the fourth most common cause of cancer deaths in women living in developed countries.2 This is because it usually takes a while for symptoms to show, and then to be diagnosed, allowing it to spread before it is discovered.

Symptoms3

The main symptoms are 

  • A swollen, painful or tender tummy
  • Sudden loss of appetite
  • Needing to pee urgently or more often

Some less common symptoms include

  • Constant tiredness
  • Unexplained weight loss 
  • Vaginal bleeding after menopause 
  • Issues with digestion, including indigestion, constipation or diarrhoea

You may be more likely to develop ovarian cancer if you have a family history, take hormone replacement therapy, or have other health issues such as endometriosis or diabetes. 

This is not an exhaustive list, and these symptoms may be linked to other disorders. Please contact your doctor if you have any concerns about your health.

Understanding immunotherapy 

How the immune system works

Your immune system is present in almost every part of your body and helps you to prevent and fight off infections. It mainly targets pathogens, which are any organism which can cause disease. This can be anything from viruses passed on by coughing, to bacteria in your food. The immune system is key in preventing sickness, or helping you if you do get sick. It is complex, made up of many different cells all working together. Some eat and digest the pathogens, while some can produce chemicals that either kill pathogens or activate other parts of the immune system.

Immunotherapy explained

Immunotherapy is a type of treatment which makes use of the complex immune system and ultimately makes it better at its job of fighting infections. 

Cancer is known for being good at hiding from immune cells using a whole host of methods, including disguising itself so it blends in with your normal, healthy cells, and altering the immune system itself, making it weaker and less able to fight back. Immunotherapy can interfere with these techniques, helping your body to fight cancer. 

Three immunotherapy options have been approved for ovarian cancer.4 To understand how these treatments work, we need to understand the immunology behind them. One type of immune cell, B cells, produces a protein called antibodies. These attach to proteins on the surface of pathogens called antigens. Antigens allow the immune system to see which cells are healthy and belong to us, and which should not be there. The process of antibodies binding to antigens is very important for several reasons, such as in the case of immunotherapy, they are very good at flagging the cancerous and damaged cells to the immune system for destruction. 

Current immunotherapies for ovarian cancer 

Monoclonal antibodies 

These are a type of antibody specifically selected in the lab to bind to a specific antigen on the surface of the particular cancer that needs treatment. It is then divided to create a huge population of the same antibody. They can then be put into the body to help the immune system by binding to the cancer cells, identifying them for other cells to kill. 

Bevacizumab is a monoclonal antibody treatment which stops the tumour from being able to grow blood vessels (a process known as angiogenesis), leading to them being starved of nutrients and unable to spread.5 This is used particularly in patients who have already received chemotherapy.6

Checkpoint inhibitors 

The immune system uses ‘checkpoints’ to make sure it’s not attacking healthy cells. When these are turned on, it is less likely to be able to identify and kill damaged cells. One of the ways cancer is good at evading the immune system is by activating these checkpoints, making the immune system less effective and allowing the cancer to go unnoticed. 

Some monoclonal antibodies are known as checkpoint inhibitors. These boost the immune system by preventing the checkpoints from being activated, so it is more likely to identify cancer and launch an attack. 

Dostarlimab is a checkpoint inhibitor which targets a process that stops a cell from dying. By blocking this, the cancer goes through cell death.7

Another checkpoint inhibitor is Pembrolizumab, which allows the immune system to recognise cancer cells more easily.8  

Advantages and challenges 

Benefits 

Immunotherapy can help the efficacy of other types of cancer treatment, such as surgery or chemotherapy.It is more targeted in nature and therefore has fewer side effects as it is specifically targeting immune cells rather than the whole body.It can prevent relapse, as it trains your immune system to fight off cancer cells if it ever returns.

Side effects

Many of the side effects are the result of your immune system damaging your body while it tries to fight the cancer off, rather than the cancer or treatment itself.9

Common side effects include:

  • Fever
  • Nausea
  • Headache
  • Fatigue 
  • Muscle pain

More severe side effects include:

  • Breathing difficulties 
  • Bleeding 
  • Heart problems  

Limitations 

The efficacy of immunotherapy is largely down to the proteins that cancer cells have on their surface. This means that if the cancer mutates and the shape of the protein changes, the antibody won’t be able to bind. 

Some checkpoint inhibitors have been found to have very limited efficacy when used alone.10

Immunotherapies are also much more expensive than other commonly used treatments.

Current research and future outlook 

Ongoing research 

There is currently a lot of work being put into clinical trials investigating other immunotherapy options for ovarian cancer. This includes other types of monoclonal antibodies and other approaches that have been effective in different types of cancer.

CAR T-cell therapy 

This is a type of ‘adoptive cell therapy’, which involves taking immune cells from the patient, modifying them to make them more effective, and then putting them back into the body.CAR T-cells are a modified type of immune cell called T cells, which are given a special CAR receptor on their surface. This makes them better at sensing their environment, and so more likely to see and destroy the cancer.11 

However, these are less effective on solid tumours as they have more variation in the proteins on their surface. They also have a tumour environment that is toxic to our cells, making it harder for the modified T cells to survive long enough to have an effect. They have also been known to cause cytokine release syndrome (CRS), which causes too many cell signalling molecules to be released causing toxic effects on the body, such as hypotension, renal damage, respiratory failure and death.12 

Cancer vaccines 

These work like other vaccines, by exposing the immune system to parts of cancer, which then induces an immune response.13 

Oncolytic virus therapy 

Viruses are intracellular pathogens, meaning they’re great at getting into cells and infecting them from within. In this treatment, viruses are changed so they specifically infect tumour cells and kill them. This also signals to the immune system that there is a danger, so it can then help with killing and the clean-up process.14

Future directions 

Biomarkers 

Immunotherapy is more effective for some patients than for others. There are currently studies underway to identify which biomarkers are best for showing which patients are most suitable for this type of treatment. This would allow treatment to be much more individualised, and therefore more likely to succeed.

Combination therapy

Immunotherapy has been proven to be more effective when used alongside other treatments. This helps tackle the issue of some treatments having low efficacy rates. Research is being conducted testing immunotherapy in combination with antiangiogenesis drugs (which stop tumours from forming blood vessels), chemotherapy, as well as a combination of multiple immunotherapy treatments.

Summary 

Immunotherapy is a very promising type of treatment for ovarian cancer, although at this stage in testing, it still has its limitations. Monoclonal antibodies can target specific cancer cells. Checkpoint inhibitors stop the cancer from being able to hide from the immune system. There are many other types of immunotherapy currently in clinical trial phases for ovarian cancer. While there are still other, more common forms of treatment, we will likely see an increase in the use of immunotherapy as it becomes more accessible in the future, working in combination to reduce the fatality rate of ovarian cancer. 

Additional resources

Support groups and resources

If you are struggling after receiving an ovarian cancer diagnosis or would like help to support a loved one through their treatment, there are many resources available. Please check out these links for support, or reach out to your doctor for further information on how to get help 

Clinical trials 

Immunotherapy trials are key in the development of new treatments, and getting them out of testing and into the lives of the people who need them. Check out this link to the cancer research institute to find out more about specific clinical trials. Always speak to your doctor about any concerns you have with your treatment.

References 

  1. Where Does Metastatic Ovarian Cancer Spread To? Moffitt n.d. https://www.moffitt.org/cancers/ovarian-cancer/faqs/where-does-metastatic-ovarian-cancer-spread-to/  (accessed December 13, 2023).
  2. Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. The Lancet 2014;348:1376–88. https://www.thelancet.com/journals/lancet/article/piiS0140-6736(13)62146-7/fulltext
  3. Ovarian cancer. NhsUk 2017. https://www.nhs.uk/conditions/ovarian-cancer/ (accessed December 12, 2023).
  4. Ovarian Cancer Immunotherapy. Moffitt n.d. https://www.moffitt.org/cancers/ovarian-cancer/treatment/immunotherapy/ (accessed December 12, 2023).
  5. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. N Engl J Med 2011;365:2473–83. https://doi.org/10.1056/NEJMoa1104390.
  6. Bevacizumab - NCI. 2006. https://www.cancer.gov/about-cancer/treatment/drugs/bevacizumab  (accessed December 12, 2023).
  7. Liu J, Gaillard S, Hendrickson AW, Moroney J, Yeku O, Diver E, et al. An open-label phase II study of dostarlimab (TSR-042), bevacizumab (bev), and niraparib combination in patients (pts) with platinum-resistant ovarian cancer (PROC): cohort A of the OPAL trial. Gynecologic Oncology 2021;162:S17–8. https://doi.org/10.1016/S0090-8258(21)00680-6.
  8. Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Annals of Oncology 2019;30:1080–7. https://doi.org/10.1093/annonc/mdz135.
  9. Bateman AC. Molecules in cancer immunotherapy: benefits and side effects. Journal of Clinical Pathology 2019a;72:20–4. https://doi.org/10.1136/jclinpath-2018-205370.
  10. Alkholifi FK, Alsaffar RM. Dostarlimab an Inhibitor of PD-1/PD-L1: A New Paradigm for the Treatment of Cancer. Medicina (Kaunas) 2022;58:1572. https://doi.org/10.3390/medicina58111572.
  11. Zhang X-W, Wu Y-S, Xu T-M, Cui M-H. CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy. Biomolecules 2023;13:465. https://doi.org/10.3390/biom13030465.
  12. Li W, Wu L, Huang C, Liu R, Li Z, Liu L, et al. Challenges and strategies of clinical application of CAR-T therapy in the treatment of tumours—a narrative review. Annals of Translational Medicine 2020;8:1093–1093. https://doi.org/10.21037/atm-20-4502.
  13. Tojjari A, Saeed Ahmed, Singh M, Cavalcante L, Sahin IH, Saeed Anwaar. A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma. Vaccines (Basel) 2023;11:1357. https://doi.org/10.3390/vaccines11081357.
  14. 14 - Li K, Zhao Y, Hu X, Jiao J, Wang W, Yao H. Advances in the clinical development of oncolytic viruses. Am J Transl Res 2022;14:4192–206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274612/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Isla Cogle

BSc Immunology student, University of Glasgow

Isla is an immunology student passionate about making science accessible to everyone. With years of experience as a science tutor and volunteer, she simplifies complex concepts and connects the public to current issues in medicine. Her dedication to education and medical communication drives her efforts to bridge the gap between research and public understanding, helping others to make informed decisions about their own health.

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