Immunotherapy for Brain Cancer

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

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

Reviewed By: David A. Reardon, M.D.
Dana-Farber Cancer Institute

Immunotherapy for brain and nervous system cancer offers potential new treatment options for a devastating set of diseases. 

Cancers of the brain and nervous system affect both adults and children, and come in several different forms. The cause of these cancers is not yet well understood. Although significant advances have been made in understanding the biology of these cancers—as well as in tumor diagnosis, treatments, and quality of life of patients with the disease—the mortality rate has remained steady for more than 30 years.

As brain tumors grow in size, they can cause a wide variety of painful and life-altering symptoms for patients with the disease, often due to the pressure these tumors inflict on the brain or the ways in which the tumors interfere with normal, healthy brain and nerve function. The majority of brain cancers are highly invasive, though this disease rarely spreads to parts of the body beyond the brain.

There are several types of brain cancer, classified by the type of cell from which they originate, including astrocytomas, gliomas, and meningiomas. Cancers of the central and peripheral nervous systems include ependymoma, neuroblastoma (which most commonly affects children ages 5 or younger), and medulloblastoma.

  • Astrocytoma originates in glial cells called astrocytes, star-shaped cells involved in cell repair and nutrient transport.
  • Ependymoma originates in ependymal cells lining the cerebrospinal fluid pathways.
  • Glioma originates in glial cells that support and protect neurons.
  • Meningioma begins in the thin membranes (called meninges) covering the brain and spinal cord.
  • Medulloblastoma originates in a region at the base of the skull called the posterior fossa.
  • Neuroblastoma arises in primitive nerve cells called neuroblasts that are found in an embryo or fetus.

Glioblastoma (GBM), which forms from astrocytes, is the most dangerous and aggressive form of brain cancer. GBM patients typically have short life expectancies after diagnosis. Only a quarter of newly diagnosed GBM patients survive for 24 months, and fewer than 10 percent of patients survive more than 5 years.

In the United States, brain and nervous system cancers account for 1 in every 100 cancer diagnoses, and are two of the primary cancers that affect children and young adults. It is estimated that 1 in 161 individuals born today will develop brain or nervous system cancer at some point in their lives. Globally, approximately 300,000 men and women are diagnosed with cancer of the brain and nervous system every year, and more than 240,000 deaths are caused by the disease. In the United States in 2019, an estimated 23,000 people were diagnosed and 17,000 died. 

In children, brain cancer is the second most common form of cancer, and accounts for 26 percent of all pediatric cancers in the United States. It is the most common form of solid tumor and the leading cause of death from cancer among children.

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Brain Cancer Treatment Options

Immunotherapy offers promising options for treating brain cancer, which is traditionally treated with chemotherapy, radiation therapy, and surgery.

In 2005, the chemotherapy temozolomide (Temodar®) was approved to treat newly diagnosed glioblastoma (GBM) patients based on a randomized phase III clinical study that showed that it added 2.5 months to the median survival of patients. However, over 50% of GBM tumors generate a DNA repair protein called MGMT (methylguanine methyltransferase) that effectively neutralizes temozolomide chemotherapy. These patients derive negligible therapeutic benefit from the addition of temozolomide to their treatment.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently three FDA-approved immunotherapy options for brain and nervous system cancers.


  • Granulocyte-macrophage colony-stimulating factor (GM-CSF): an immunodulatory cytokine; approved in combination with naxitamab-gqgk for a subset of patients with advanced neuroblastoma
  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced brain or nervous system cancers that have high microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H)

Targeted Antibodies

  • Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for advanced glioblastoma
  • Dinutuximab (Unituxin®): a monoclonal antibody that targets the GD2 pathway; approved for first-line treatment of high-risk pediatric neuroblastoma
  • Naxitamab-gqgk (Danyelza®): a monoclonal antibody that targets the GD2 pathway; approved in combination with GM-CSF for a subset of patients with advanced neuroblastoma

Several other immunotherapies are being used to treat different types of brain cancers in clinical trials.

Find a brain cancer clinical trial

CRI's Impact in Brain Cancer

Despite significant advances in the understanding of brain cancer, and improvements to diagnosis, treatments, and patient quality of life, the mortality rate for brain cancer has remained consistent for more than three decades. Support for immunology research focused on this aggressive and tragic disease is urgently needed.

  • CRI has opened a phase 2 trial to test the efficacy and safety of durvalumab (MEDI4736), an anti-PD-L1 antibody being developed by MedImmune/AstraZeneca, in patients with glioblastoma (NCT02336165), with David A. Reardon, M.D., Dana-Farber Cancer Institute, as principal investigator.
  • Adam Williamson, Ph.D., a CRI postdoctoral fellow at the University of California, San Francisco, is studying how glial cells recognize and digest dead cells from a brain tumor in order to reduce the harmful inflammation that causes death of surrounding neurons.
  • Bryan Choi, the recipient of a Student Training and Research in Tumor Immunology (STaRT) grant at Duke University, designed a bi-specific T cell-engaging antibody (BiTE) against the EGFRvIII tumor-specific antigen, which is expressed in a majority of glioblastoma cases, and has performed preclinical tests to determine its efficacy against EGFRvIII-expressing glioblastoma.
  • With funding from a CRI Investigator Award, Alex Yee-Chen Huang, M.D., Ph.D., at Case Western Reserve University, developed an innovative approach to tracking the activity and interactions of immune and tumor cells in real time in models of pediatric and adult brain cancers, including medulloblastoma and glioma.

New and developing brain cancer immunotherapies have the potential to reduce the harmful effects and improve survival rates for patients with brain cancer. You can explore CRI’s current research into brain cancer in our funding directory.

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Featured Patient

What I loved is that there were no weird foreign medicines in it. It was everything from me, just put back in.

Brad Silver
Brain Cancer  |  Diagnosed 2003
Read My Story
Featured Scientist
Robert M. Prins, Ph.D.
University of California, Los Angeles
CLIP Investigator  |  2018
View Funding Profile

Brain Cancer Statistics

300K Newly diagnosed patients each year globally
240K Deaths each year globally

Brain and Nervous System 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
  • 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 brain cancer clinical trials include:

  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • GD2: a pathway that controls cell growth, adhesion, and migration, and is often abnormally overexpressed in cancer cells
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and  associated with 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 brain cancer clinical trials include:

  • MUC1: a sugar-coated protein that is commonly overexpressed in cancer
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • Tumor-associated antigens: proteins often expressed at abnormally high levels on tumor cells and 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 brain cancer clinical trials include:

  • GD2: a pathway that controls cell growth, adhesion, and migration, and is often abnormally overexpressed in cancer cells
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and  associated with metastasis
  • Tumor-associated antigens: proteins expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels

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 brain 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
  • 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

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 brain 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
  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Measles: a highly contagious virus that infects the respiratory tract and can cause measles
  • Vaccinia virus: a virus that belongs to the poxvirus family and can cause smallpox in humans
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Sources: ACS Facts and Figures 2019, Cedars Sinai Brain Tumors and Brain Cancer webpage; CRI grantee progress reports and other CRI grantee documents; GLOBOCAN 2018; National Cancer Institute

Updated August 2020

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

*Immunotherapy results may vary from patient to patient.