Donate

Immunotherapy for Lung Cancer

Immunotherapy Immunotherapy by Cancer Type

Let's spread the word about Immunotherapy! Click to share this page with your community.

Copy Link

Lung Cancer

Treatment Options

CRI's Impact

Clinical Trials

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

Reviewed by: Matthew Hellmann, M.D.

Details

Memorial Sloan Kettering Cancer Center

Immunotherapy for lung cancer, alone or in combination with conventional treatments, can significantly improve outcomes for patients fighting lung cancer.

As the most common cancer worldwide, lung cancer impacts approximately 2.1 million people—and causes an estimated 1.7 million deaths—each year and is the leading cause of cancer-related deaths for both men and women. In the United States alone, there were an estimated 236,000 new lung cancer cases along with 132,000 deaths in 2021. Lung cancer claims more lives every year than do cancers of the breast, prostate, and colon combined.

Lung cancer is subdivided into two major types:

Small cell lung cancer (SCLC) comprises approximately 10-15% of all known lung cancer cases.
Non-small cell lung cancer (NSCLC) comprises approximately 85-90% of all known lung cancers cases.
- Adenocarcinoma arises from cells in the lung that secrete substances such as mucus (40% of lung cancers).
- Squamous cell (epidermoid) carcinoma arises from the flat squamous cells that line the inside of the airways of the lung (25-30% of lung cancers).
- Large cell (undifferentiated) carcinoma typically arises from the epithelial cells that line the outer regions of the lung (10-15% of lung cancers).
Mesothelioma arises from a thin layer of tissue that covers many organs and most commonly occurs around the lungs.

When most lung cancer patients become symptomatic and are diagnosed, the disease has already advanced to late stage (at stage 3b/4 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. Fortunately, immune-based cancer treatments are helping to improve chances of living longer for patients with lung cancer.

Subscribe to email alerts

Lung Cancer Treatment Options

Until recently, conventional treatment options for lung cancer included surgery, chemotherapy, and radiation. Since the majority of lung cancer patients are diagnosed with advanced disease (stage 3b/4), these treatments are unlikely to result in complete cures, though they may significantly improve survival and provide symptom relief.

In 2015, the U.S. FDA approved the first immunotherapy to treat a subset of lung cancer patients. Immunotherapy is class of treatments that helps a person’s own immune system eliminate or control cancer. Recent clinical studies treating patients with immunotherapy, either alone or in combination with other treatments, have demonstrated significant patient improvement, resulting in FDA approval of several other immunotherapy options for more lung cancer patients, including approvals to treat patients with immunotherapy as a first-line therapy instead of conventional treatments.

Targeted Antibodies

Amivantamab (Rybrevant™): a bispecific antibody that targets EGFR and MET receptors on tumor cells; approved for subsets of patients with non–small cell lung cancer (NSCLC)
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
Ramucirumab (Cyramza®): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with 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 patients with advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), including as a first-line therapy in combination with chemotherapy.
Cemiplimab (Libtayo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for a subset of patients with advanced non–small cell lung cancer (NSCLC)
Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced lung cancer that has DNA mismatch repair deficiency (dMMR)
Durvalumab (Imfinzi®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with stage III non-small cell lung cancer (NSCLC) who have completed chemoradiation, as well as patients with advanced small cell lung cancer (SCLC) in combination with chemotherapy.
Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved, in combination with nivolumab, as a first-line treatment, both with or without chemotherapy, for patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma
Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma in combination with ipilimumab, with or without chemotherapy
Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy its own or in combination with chemotherapy

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 immunotherapy for lung cancer. 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:

The benefits of anti-PD-1 checkpoint immunotherapy prior to surgery in patients with advanced lung cancer, highlighted in a recent study led by members of the CRI-SU2C Dream Team
The connection between the number of genetic mutations of lung tumors and patient responses to treatment with anti-PD-1 checkpoint immunotherapy, discovered by a team led by Naiyer Rizvi, M.D., of Columbia University Medical Center
A “human breathing lung-on-a-chip” device, developed by Technology Impact Award recipient Dan Huh, Ph.D., of the University of Pennsylvania, that is capable of mimicking normal lung biology and allowing for in-depth characterization of how various factors affect disease
A vaccine targeting the NY-ESO-1 antigen, developed through the CRI/Ludwig Cancer Antigen Discovery Collaborative, that led to responses in lung cancer patients
A clinical study, funded by the CRI Clinical Accelerator, that uses blood tests to detect circulating tumor DNA (ctDNA) in NSCLC patients on treatment with pembrolizumab to better understand patient response and treatment regimen

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

I am fearfully and wonderfully made, no weapon formed against me shall prosper.

K.C. Dill

Lung Cancer | Diagnosed 2015

Ready My Story

Featured Scientist

Asya Rolls, Ph.D.

Israel Institute of Technology

Grantee | 2020

View Funding Profile

Understand How Immunotherapy Works

Lung Cancer Statistics

1 in 4	Cancer-related deaths caused by lung cancer
#1	Leading cause of cancer deaths among both men and women
Approx. 80%	Of lung cancer caused by cigarette smoking
2.1	Million newly diagnosed patients each year globally

Lung Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new lung 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 can become reactivated in cancer cells, flagging them as abnormal to the immune system
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 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 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

Find an immunotherapy clinical trial

Begin the Process

Create a profile and fill out a questionnaire to identify immunotherapy clinical trials for which you may be eligible.

Need more information? Learn more about clinical trials.

News & Events

April 14, 2022

AACR 2022 Recap

At the 2022 AACR annual meeting, CRI scientists highlighted a wide scope of cancer immunology advances, and brought myeloid cells to the forefront of the field.

Read Article

March 30, 2022

FDA Immunotherapy Approvals in 2022

As drug development in cancer immunotherapy has accelerated, the U.S. Food and Drug Administration has made several new approvals in 2022.

Read Article

November 29, 2022

Giving Tuesday 2022

Be a part of the global generosity movement and celebrate all acts of giving. #Giv...

September 06, 2022

CRI to Host Second Annual Spanish-Language Virtual Immunotherapy patient Summit

The free online event will connect cancer patients and caregivers with the latest ...

Read Release

Sources: ACS Facts and Figures 2021; GLOBOCAN 2018; World Health Organization

Updated September 2021

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

*Immunotherapy results may vary from patient to patient.

Cancer Research Institute | National Headquarters
29 Broadway, Floor 4 | New York, NY 10006-3111

800-992-2623 212-832-9376 Staff Directory

Stay Connected with CRI

Recent Blog Posts

Dr. Benjamin Vincent recaps highlights from Day 4 of the 2022 CRI-ENCI-AACR International Cancer Immunotherapy Conference, covering cancer vaccines and innovative technologies to study tumor immunity.

Dr. E. John Wherry dicusses cell therapies and the cancer ecosystem during Day 3 of the 2022 CRI-ENCI-AACR International Cancer Immunotherapy Conference (CICON22).

Top