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Immunotherapy for Stomach Cancer

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

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

Reviewed By: Joseph Chao, M.D.
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City of Hope
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While the number of people in the United States diagnosed with stomach cancer, or gastric cancer, is declining, this disease is the fifth most common cancer diagnosis worldwide and the third most deadly. About 90% to 95% of cancers of the stomach are adenocarcinomas. These cancers develop from the cells that form the innermost lining of the stomach. Other types of stomach cancer are gastrointestinal carcinoid tumors and gastrointestinal stromal tumors.

Untreated infection with bacteria called H. pylori is a potential cause of gastric cancer. Other stomach cancer risk factors may include smoking and a diet of highly processed or salty foods.

Worldwide, there are nearly one million new cases diagnosed each year and 780,000 deaths annually. In 2018, an estimated 26,000 people were diagnosed with stomach cancer in the United States alone, where it caused roughly 11,000 deaths. This represents a substantive change since the very first estimates in 1975, when stomach cancer was the most common cancer. The reasons for this decline are not completely known, but may be linked to increased use of refrigeration for food storage.

In countries where stomach cancer is more common, public mass screenings for the disease have aided in diagnosing more cases during the disease's early stages—when survival rates are drastically higher. When stomach cancer has metastasized, the 5-year survival rate falls to just 5%.

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Stomach Cancer Treatment Options

Treatment of stomach cancer depends on where the disease initiated and the extent of its spread throughout the body. If diagnosed early, surgery is the first-line treatment for stomach cancer, sometimes in combination with chemotherapy and/or radiation treatment. For advanced stomach cancer, treatment aims to stabilize disease progression and improve patients’ prognosis.

There are currently three approved immunotherapy options for stomach cancer.

Targeted Antibodies

  • Ramucirumab (Cyramza®): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced stomach or gastroesophageal cancer
  • Trastuzumab (Herceptin®): a monoclonal antibody that targets the HER2 pathway; approved for subsets of patients with advanced, HER2-positive gastroesophageal cancer

Immunomodulators

  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced, PD-L1-positive stomach or gastroesophageal cancer

Several other immunotherapies—including checkpoint inhibitors, CAR T cell treatments, and multiple antibody approaches—are also being investigated in clinical trials and could soon provide stomach cancer patients with even more approved immunotherapy options.

Find a stomach cancer clinical trial

CRI's Impact in Stomach Cancer

At the Cancer Research Institute, we're dedicated to advancing immunotherapy as a viable treatment for patients with stomach cancer. CRI funding of recent and ongoing studies of immune-based stomach cancer therapies includes the use of NY-ESO-1 in therapeutic vaccines and studies into B7x-targeting antibodies (an immune checkpoint molecule overexpressed in stomach cancer) as a promising therapy for numerous different cancer types.

  • CRI researchers, including Lloyd J. Old, M.D., and Sacha Gnjatic, Ph.D., analyzed cancer-testis (CT) antigen expression in gastric cancer and found that two CT antigens, NY-ESO-1 and MAGE-3, were expressed in 11.9% and 41.65%, respectively, in these cancers. Additionally, an immune response to NY-ESO-1 was detected in 6 out of 12 gastric cancer patients, indicating that it could potentially be a useful target for therapeutic vaccines.
  • The CRI-SU2C Cancer Immunology Dream Team at Memorial Sloan Kettering Cancer Center, led by Michel Sadelain, M.D., Ph.D., is taking a new approach to chimeric antigen receptor (CAR) T cell therapy in the lungs, and if proven to be successful, this approach can be extended to other mesothelin-expressing cancers, such as gastric cancer.
  • Vladimir Vigdorovich, Ph.D., a CRI postdoctoral fellow at Albert Einstein College of Medicine, and colleagues developed a system to screen monoclonal antibodies directed at B7x (an immune checkpoint molecule) and found one that inhibited the growth of B7x-expressing tumors.

See what stomach cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way cancer is treated forever—curing more people and saving more lives.

Donate to stomach cancer research 

Featured Patient

When I was in the hospital, I made a vow that when I was through with “this,” I would make a difference in the lives of others.

TJ Sharpe
Melanoma  |  Diagnosed 2012
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Padmini S. Pillai, Ph.D.
Massachusetts Institute of Technology
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Stomach Cancer Statistics

65% 5-year survival rate for localized disease
0.8% Of Americans will be diagnosed with stomach cancer
1 Million newly diagnosed cases each year globally

Stomach 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 stomach cancer clinical trials include:

  • cMET: a growth-related pathway that is often abnormally activated in cancer
  • DLL/Notch: a pathway that can promote cell growth
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • FGF/FGF-R: a pathway that controls cell growth, death, and migration
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • 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 stomach cancer clinical trials include:

  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • 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

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 stomach cancer clinical trials include:

  • CEA: a protein involved in cellular adhesion normally produced only before birth; often abnormally expressed in cancer and may contribute to metastasis
  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in cancer cells, flagging them as abnormal to the immune system

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 stomach cancer clinical trials include:

  • CD40: activating this co-stimulatory pathway can kickstart adaptive immune responses
  • CD137 (also known as 4-1BB): activating this co-stimulatory pathway can help promote the growth, survival, and activity of cancer-fighting T cells
  • 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: an intracellular signaling protein that can help stimulate adaptive immune responses

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 stomach cancer clinical trials include:

  • Maraba virus: a virus found exclusively in insects
  • 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: ACS Facts & Figures 2018; ClinicalTrials.gov; CRI documents; GLOBOCAN 2018; National Cancer Institute (NCI); NCI Physician Data Query (PDQ); National Comprehensive Cancer Network (NCCN) Guidelines for Patients

Updated February 2019

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

*Immunotherapy results may vary from patient to patient.

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