Immunotherapy for Uterine Cancer

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  • Uterine (Endometrial) Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy for Uterine Cancer Changing the Outlook for Patients?

Reviewed By: Kunle Odunsi, M.D., Ph.D.
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Roswell Park Comprehensive Cancer Center
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Immunotherapy for uterine (endometrial) cancer is an emerging area of research and treatment, especially for patients with advanced cases.

Uterine cancer, also known as endometrial cancer, occurs when cells that line the inside of the uterus start to grow uncontrollably. Cancer can develop in the upper part (uterine corpus), commonly referred to as uterine cancer, or the lower part (uterine cervix), commonly referred to as cervical cancer.

Common risk factors associated with uterine cancer include obesity, hormonal shifts in estrogen production, age, diets high in fat, diabetes, family history of certain cancers, and prior breast or ovarian cancer. The National Comprehensive Cancer Network recommends universal mismatch repair protein testing or microsatellite instability (MSI) testing of uterine cancers.

Uterine cancer is the sixth most common form of cancer in women and the fifteenth most common cancer type overall. Worldwide, approximately 382,000 new cases are diagnosed every year and there are an estimated 90,000 deaths. Of these, the United States accounts for approximately 65,500 of these new cases and 12,600 deaths. The prognosis of endometrial carcinoma is determined primarily by disease stage, grade, and histology. The five-year survival rate for individuals diagnosed with stage 1 disease is approximately 80 to 90 percent, for stage 2 it is 70 to 80 percent, and for stages 3 and 4 it is 20 to 60 percent.  

If detected early, uterine cancer is easy to treat, but new treatment options are needed for patients with advanced cases and for patients wishing to avoid surgery and keep their reproductive systems intact.

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Uterine Cancer Treatment Options

Standard treatments for uterine cancer include surgery, radiation therapy, hormone therapy, targeted therapy, and chemotherapy. Immunotherapy is an emerging area of research and treatment for endometrial cancer.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There is currently one FDA-approved immunotherapy for the treatment of uterine cancer.

Immunomodulators

  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced endometrial cancer, including those with tumors with high microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); also approved in combination with lenvatinib for advanced/recurrent endometrial cancer regardless of MSI or TMB status

Other immunotherapies are also currently being tested in clinical trials, which patients of any type or stage of uterine cancer are encouraged to explore.

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CRI's Impact in Uterine Cancer

Since 1953, the Cancer Research Institute has dedicated more than $10 million in funding to develop and discover immunotherapies that can treat gynecologic cancers, including uterine cancer. Research findings from leading immunologists continue to demonstrate potential and promise for the future of immune-based treatment for patients with uterine cancer.

  • In 2018, the CRI Clinical Accelerator launched a clinical trial to evaluate the effectiveness of PD-1 inhibitors plus or minus CTLA-4 inhibitors in patients with advanced solid tumors that have failed standard therapy.
  • In 2018, CRI fellow Monica Olcina, Ph.D., revealed that mutations in the complement pathway occur at higher frequencies compared to other mutations in uterine cancer and are associated with poor survival.

You can explore CRI’s current funding for uterine cancer research in our funding directory.

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Uterine (Endometrial) Cancer Statistics

382k new cases every year
6th Most common form of cancer in women

Uterine 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.

Therapies
  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunomodulators
  • 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 uterine cancer clinical trials include:

  • DKK1: a secreted protein involved in migration, self-renewal, and blood vessel formation
  • 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
  • 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 uterine cancer clinical trials include:

  • MUC-1: a sugar-coated protein that is commonly overexpressed in cancer
  • NY-ESO-1: a protein that is normally produced only before birth and in adult testes, but is often abnormally expressed in cancer
  • Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
  • 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

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 uterine cancer clinical trials include:

  • 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
  • NY-ESO-1: a protein that is normally produced only before birth and in adult testes, 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 uterine cancer clinical trials include:

  • 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
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • PD-1/PD-L1: blocking this pathway can help prevent “exhaustion” in cancer-fighting T cells and enable continued immune responses against tumors

Oncolytic virus therapy uses viruses that are often, but not always, modified in order to 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 uterine 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
  • Vesicular Stomatitis Virus: a virus that belongs to the same family as the rabies virus; can cause flu-like symptoms in humans
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Sources: ACS Facts and Figures 2020; American Cancer Society; Cancer.net; CRI documents; GLOBOCAN 2018; National Cancer Institute; World Cancer Research Fund

Updated September 2020

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

 

*Immunotherapy results may vary from patient to patient.

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