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Immunotherapy for Lung Cancer

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

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

Reviewed By: Naiyer A. Rizvi, M.D.
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NewYork-Presbyterian/Columbia University Medical Center, New York, NY
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As the most common cancer type across the globe, lung cancer impacts approximately 2 million people each year and is the leading cause of cancer-related deaths for both men and women in the world. Lung cancer claims more lives every year than do breast, prostate, and colon cancer combined.

Lung cancer is subdivided into two major types: 

  • Non-small cell lung cancer (NSCLC) comprises approximately 85-90% of all known lung cancers cases.
    • The majority of NSCLCs, approximately 25-30%, are the non-squamous type, meaning that they that arise from cells other than the flat squamous cells that line the inside of the airways of the lung. 
    • Adenocarcinomas, which arise from cells in the lung that secrete substances such as mucous, comprise approximately 40% of NSCLCs.
  • Small cell lung cancer (SCLC) comprises approximately 10-15% of all known lung cancer cases.

When most lung cancer patients become symptomatic and are diagnosed, the disease has already advanced to late stage (at stage IIIb/IV or higher). At these stages, surgery, chemotherapy, and radiation are only minimally effective. New treatments are needed for patients facing an advanced lung cancer diagnosis. For this reason, lung cancer is one of the major cancer types for which new immune-based cancer treatments are currently in development.

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Lung Cancer Treatment Options

Conventional treatment options for lung cancer include surgery, chemotherapy, and radiation. Since the majority of lung cancer patients are diagnosed with advanced disease (stage IIIb/IV), conventional treatment options are unlikely to result in complete cures, though they may significantly improve survival and provide symptom relief. Recent clinical studies are encouraging, and show that immunotherapy alone or in combination with conventional treatments can significantly improve patient outcomes. These successes have resulted in FDA approval of six immunotherapy options for certain lung cancer patients.

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 non-small cell lung cancer (NSCLC), including as a first-line therapy
  • Necitumumab (Portrazza®): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy

Immunomodulators

  • Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC)
  • Durvalumab (Imfinzi™): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC)
  • Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC) as well as those with metastatic small cell lung cancer (SCLC) that has advanced following treatment with platinum-based chemotherapy and at least one other line of treatment
  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy

These checkpoint immunotherapy approvals were landmark events for the treatment of lung cancer. With these immunotherapies, many advanced-stage lung cancer patients are starting to see long-lasting remissions and longer survival rates. Several immunotherapy agents are currently being tested in lung cancer clinical trials

Find a lung cancer clinical trial

CRI's Impact in Lung Cancer

Since its founding, the Cancer Research Institute (CRI) has dedicated numerous grants and fellowships to the research of lung cancer immunotherapy. We continue to fund the science of immune-based therapies for lung cancer, supporting the best scientists working to advance the field of this promising treatment.

CRI-funded discoveries and breakthroughs, along with ongoing studies, include: 

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

Donate to lung cancer research

Featured Patient

The intention of the trial was not to cure me. It was to treat my cancer like you treat diabetes—that as long as you take your medicine you're going to be fine.

Bob Carlson
Lung Cancer  |  Diagnosed 2011
Read My Story
Featured Scientist
Stanley R. Riddell, M.D.
Fred Hutchinson Cancer Research Center
Grantee  |  2013
View Funding Profile

Lung Cancer Statistics

1 in 4 Cancer-related deaths caused by lung cancer
#1 Leading cause of cancer deaths among both men and women

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Lung 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 lung 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
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • PDGFRα: a surface receptor that plays a role in stimulating cell division and growth
  • 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 lung 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
  • 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
  • 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 lung 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
  • ROR1: an enzyme that is normally produced only before birth, but is often abnormally expressed in cancer and may promote cancer cell migration as well as prevent cancer cell death
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

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 lung 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
  • GITR: activating this pathway can help prevent immunosuppression and increase the survival of cancer-fighting T cells 
  • ICOS: activating this co-stimulatory pathway on T cells can help enhance immune responses against cancer
  • 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 lung 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
  • Coxsackie virus: a virus that belongs to the same group as the polio virus; commonly infects young children and causes flu-like symptoms
  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Maraba virus: a species of the Vesiculovirus family 
  • Measles virus: the virus that causes measles, an infection of the respiratory system
  • Picornavirus: a family of viruses that can cause a range of diseases in mammals and birds
  • Reovirus: a family of viruses that can infect plants, animals, and fungi, but are not known to be associated with any diseases
  • 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: American Cancer Society, World Health Organization

Updated September 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.

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