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Immunotherapy for Ovarian Cancer

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  • Ovarian Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy Changing the Outlook for Patients with Ovarian Cancer?

Reviewed By: Kunle Odunsi, M.D., Ph.D.
Roswell Park Cancer Institute, Buffalo, NY

Ovarian cancer often progresses significantly before a patient is diagnosed. This is because the symptoms of ovarian cancer can be easily confused with less life-threatening digestive issues such as bloating, constipation, and gas. Roughly only 20 percent of ovarian cancers are detected before it spreads beyond the ovaries.

The most prominent risk factor for this disease is a family history that includes breast or ovarian cancer. Women who test positive for the inherited mutations in the BRCA1 or BRCA2 genes are at significantly greater risk—45% to 65% risk of developing breast cancer and 10% to 20% risk of developing ovarian cancer by age 70. Women at age 40 are at the highest risk.

Ovarian cancer is the leading cause of death from gynecologic cancer in the United States, affecting more than 22,000 women each year, with over 14,000 deaths resulting from the disease. Globally, ovarian cancer affects more than 300,000 women each year.

While significant advances have been made in surgical and chemo-based treatments for ovarian cancer, the survival rates have only modestly improved. The poor survival in advanced ovarian cancer is due both to late diagnosis as well as to the lack of effective second-line therapy for patients who relapse. Many women affected by advanced ovarian cancer respond to chemotherapy, but effects are not typically long-lasting. The clinical course of ovarian cancer patients is marked by periods of remission and relapse of sequentially shortening duration until chemotherapy resistance develops. More than 80% of ovarian cancer patients experience recurrent disease, and more than 50% of these patients die from the disease in less than five years post-diagnosis.

There is an urgent need for new treatments for advanced stage, recurring ovarian cancer.

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Ovarian Cancer Treatment Options

First-line treatment for ovarian cancer includes surgery followed by a chemotherapy regimen combining a platinum-based (usually carboplatin) and a taxane-based (usually paclitaxel) treatment. This course of treatment leads to a complete response in approximately 80% of patients. A complete response means no visible evidence of disease on imaging scans and normal blood tests.

Patients who initially respond to treatment but then relapse after a period of six months or more may undergo the same therapy. Patients who progress during first-line treatment or who relapse within six months following successful first-line treatment are considered refractory or resistant to platinum-based treatments. For these patients, there are several chemotherapeutic options; however, each has shown only marginal benefit.

There is currently one approved immunotherapy option for ovarian cancer.

Targeted Antibodies

  • Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced ovarian cancer

Women with stage 1 tumors (for whom survival is greater than 95% after comprehensive surgery), do not generally need to consider clinical trials. Patients with platinum-resistant, recurrent ovarian cancer, or all stages of ovarian cancer above stage I/grade I, should consider entering into immunotherapy clinical trials.

Find an Ovarian Cancer Clinical Trial

CRI's Impact on Ovarian Cancer

Since 1985, the Cancer Research Institute has dedicated more than $21 million in grant funding to discover and develop effective immunotherapies to treat ovarian cancer. CRI-funded scientists have shown that the presence of the immune system’s T cells in ovarian tumors is strongly correlated with improved survival in these patients.

Research findings from leading immunologists continue to demonstrate potential and promise for the future of immune-based treatment for patients with ovarian cancers—bringing hope and optimism for more lifesaving therapies for this formidable disease.

  • George Coukos, M.D., Ph.D., a member of the CRI clinical trials network and a professor at the University Hospital of Lausanne, Switzerland, is leading a phase I/II trial of durvalumab (IMFINZI®, MedImmune/AstraZeneca), an anti-PD-L1 checkpoint inhibitor, and motolimod, a Toll-like receptor 8 agonist, for patients with recurrent, platinum-resistant ovarian, peritoneal, or fallopian tube cancer for whom doxorubicin is indicated.
  • In a study by CRI investigator Kunle Odunsi, M.D., Ph.D., at Roswell Park Comprehensive Cancer Center, patients in first remission treated with a NY-ESO-1 cancer vaccine showed a median time to progression of 21 months compared with a historical average of 16 months.
  • Members of the Ovarian Cancer Working Group Danila Valmori, Ph.D., at the Centre de Lutte Contre le Cancer-Nantes Atlantique, and Maha Ayyoub, Ph.D., at the Institut Gustave-Roussy, in France, have made important discoveries about the roles and characteristics of different immune cells in ovarian cancer, including the Th17 subset of helper T cells and regulatory T cells.
  • David Lampi Hermanson, Ph.D., a recent CRI postdoctoral fellow at the University of Minnesota, produced Natural Killer immune cells from stem cells, inserting a chimeric antigen receptor (CAR) capable of recognizing mesothelin, a protein that is expressed in 70% of ovarian cancer patients.
  • Juan R. Cubillos-Ruiz, Ph.D., a former CRI postdoctoral fellow and CRI CLIP Investigator at Weill Cornell Medical College, has found a protein, XBP1, that may represent a highly promising target for immunotherapies aimed at boosting pre-existing anti-ovarian cancer immune responses. More recently, Dr. Cubillos-Ruiz revealed how endosplasmic reticulum stress can contribute to the suppression of immune responses against ovarian cancer.

Learn more about our current funding for ovarian cancer research.

Donate to Ovarian Cancer Research

Featured Patient

You don’t think that you can just have cancer in your body and be okay. But as long as it doesn’t grow, and it’s not anywhere that’s causing you issues, then you can.

Denise Zackman
Ovarian Cancer  |  Diagnosed 2007
Read My Story
Featured Scientist
Hideho Okada, M.D., Ph.D.
University of California, San Francisco
Clinical Accelerator  |  2015
View Funding Profile

Ovarian Cancer Statistics

#1 Leading cause of death from gynecological cancers in the US
9 out of 10 Ovarian cancers are epithelial cancers
80% Of ovarian cancer patients will see recurrence of disease

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Ovarian Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunodulators
  • Oncolytic Virus Therapy

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in ovarian cancer clinical trials include:

  • Angiopoietin: this pathway can promote the growth of blood vessels in tumors
  • DLL/Notch: a pathway that can promote cell growth
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • RANKL: a protein that plays a role in bone regeneration and modeling, and is often overexpressed in cancer
  • TROP2: a protein that is commonly overexpressed in cancer and appears to aid cancer cell self-renewal, proliferation, invasion, and survival
  • VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in ovarian cancer clinical trials include:

  • 5T4: an antigen often expressed by several different types of cancers
  • CEA: a protein involved in cellular adhesion normally produced only before birth; often abnormally expressed in cancer and may contribute to metastasis
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • Folate-related proteins:  proteins in this pathway are commonly overexpressed in cancer
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • MUC-1: a sugar-coated protein that is commonly overexpressed in cancer
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
  • P53: a tumor suppressor protein that is often mutated, nonfunctional, and overexpressed in cancer
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
  • Telomerase: an enzyme that helps maintain the health of cellular DNA; exploited by cancer cells to achieve immortality
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in ovarian cancer clinical trials include:

  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but deregulated cancer cells often reactivate their expression
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in ovarian cancer clinical trials include:

  • CD40: activating this co-stimulatory pathway can kick start adaptive immune responses
  • CD73 or A2AR: blocking these pathways can help prevent the production of immunosuppressive adenosine
  • CD137 (also known as 4-1BB): activating this co-stimulatory pathway can help promote the growth, survival, and activity of cancer-fighting T cells
  • CSF1/CSF1R: blocking this pathway can help reprogram cancer-supporting macrophages
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • CXCR4: blocking this pathway can promote the migration and recruitment of immune cells
  • GITR: activating this pathway can help prevent immunosuppression and increase the survival of cancer-fighting T cells
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • OX40: activating this co-stimulatory pathway can help promote T cell survival after activation
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
  • STAT3: activating this intracellular signaling protein can help stimulate adaptive immune responses
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses modified viruses that can infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in ovarian cancer clinical trials include:

  • Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
  • Measles virus: a highly contagious virus that infects the respiratory tract and can cause measles
  • Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
  • Vaccinia Virus: the virus that was used to help vaccinate against and eliminate smallpox; rarely causes illness in humans and is associated with a rash covering the body
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Sources: National Cancer Institute Physician Data Query (PDQ); American Cancer Society Facts & Figures 2016; GLOBOCAN 2012; National Comprehensive Cancer Network (NCCN) Guidelines for Patients;; CRI grantee progress reports and other grantee documents; GLOBOCAN2018

Updated November 2018

*Immunotherapy results may vary from patient to patient. Consult a healthcare professional about your treatment options.

*Immunotherapy results may vary from patient to patient.