CAR T Cells and Lung Cancer: Could This Immunotherapy Become a Future Treatment?
CAR T cell therapy has transformed the treatment of some blood cancers, offering long-lasting responses for people who previously had few treatment options. Naturally, many people affected by lung cancer ask the same question:
Could CAR T cells also become a treatment for lung cancer?
The short answer is not yet.
Although CAR T therapy is not currently a standard treatment for lung cancer, researchers around the world are working to overcome the challenges that have limited its success in solid tumours. New research published in Nature Cancer marks another step forward, showing how scientists are identifying better targets for CAR T therapy and moving promising treatments from the laboratory into early clinical testing.
This article explains what CAR T cells are, why lung cancer presents such a difficult challenge, and what the latest research could mean for the future.
Key takeaways
CAR T therapy has been highly successful in several blood cancers but is not yet a routine treatment for lung cancer.
Lung cancer is more difficult because tumours are diverse and finding a safe target is challenging.
Researchers are developing new ways to identify proteins that can be safely targeted by CAR T cells.
A new Nature Cancer study provides evidence that this approach may help advance CAR T therapy for solid tumours, although it did not include people with lung cancer.
Clinical trials continue to explore whether CAR T therapy can eventually become part of lung cancer treatment.
What are CAR T cells?
Your immune system already contains specialised white blood cells called T cells. Their job is to recognise and destroy infected or abnormal cells, including cancer cells.
CAR T cell therapy takes some of these T cells from a person’s blood and genetically modifies them in a laboratory. The modified cells are given a new receptor, called a chimeric antigen receptor (CAR), which acts like a highly specific GPS system, helping them recognise a particular protein on cancer cells. Once the modified cells are returned to the body, they can seek out and attack cells carrying that target.
This approach has transformed treatment for several blood cancers, including some forms of leukaemia and lymphoma. For some people, it has produced long-lasting responses when other treatments have stopped working.
So why hasn’t the same happened in lung cancer?
Why is lung cancer so much harder to treat with CAR T cells?
Blood cancers and solid tumours are very different.
In many blood cancers, nearly every cancer cell carries the same identifying protein. This gives CAR T cells a clear target.
Lung cancer is much more complicated.
Researchers have to overcome several major challenges before CAR T therapy can become a routine treatment.
Finding the right target
Perhaps the biggest challenge is identifying a protein that is found on cancer cells but not on healthy tissue.
If CAR T cells attack a protein that is also present in normal organs, they can damage healthy cells as well as cancer cells.
This is one of the main reasons CAR T therapy has been slower to develop for solid tumours such as lung cancer.
Every tumour is different
No two lung cancers are exactly alike.
Even within the same tumour, different groups of cancer cells may have different genetic changes and produce different proteins. If CAR T cells only recognise one target, some cancer cells may escape treatment.
The tumour microenvironment
Lung tumours do more than grow.
They create a surrounding environment that suppresses the immune system. Cancer cells can recruit other cells that reduce immune activity, produce signals that switch T cells off, and make it difficult for immune cells to reach the tumour.
Researchers often describe this as an immunosuppressive tumour microenvironment.
Even highly effective CAR T cells may struggle to work if they become exhausted or inactive soon after reaching the tumour.
Cancer changes over time
Cancer is not static.
As treatment continues, tumours evolve. Some cells disappear, while others develop new genetic changes that allow them to survive.
This means a target that looks ideal when treatment begins may become less useful later if cancer cells stop producing it.
For CAR T therapy to work well, researchers need targets that remain stable over time.
So what has changed?
This is where the new Nature Cancer study becomes interesting.
Rather than asking whether an existing protein could be targeted, researchers began by asking a different question:
Can we find proteins that are switched on by the cancer itself and remain present throughout the disease?
The team studied a rare cancer driven by a specific gene fusion and identified a protein called GPNMB that was highly and consistently expressed across tumour samples. They then developed a CAR T therapy directed against this target, tested it extensively in laboratory models and progressed to a first-in-human clinical study.
An accompanying independent News & Views article describes this as an important step because identifying suitable targets remains one of the biggest obstacles to developing CAR T therapies for solid tumours. Interestingly, it also highlights a separate study in glioblastoma that independently identified GPNMB as a promising CAR T target, strengthening confidence that this protein deserves further investigation.
Further reading
What Could a New Iron Discovery Mean for Lung Cancer Immunotherapy?
Explores how scientists are trying to improve cancer immunotherapy by helping immune cells remain active inside tumours. A good companion to understanding why CAR T cells often struggle in solid tumours.
Lung Cancer Biomarker Testing Is Moving Faster Than Ever
Explains why biomarker testing is becoming increasingly important in guiding treatment decisions and future personalised therapies.
The Microbiome and Lung Cancer: How Gut Bacteria Could Change Treatment
Looks at growing evidence that the gut microbiome may influence how well some cancer treatments, including immunotherapy, work.
Understanding the Environment Around Lung Cancer Cells
Find out how the tumour microenvironment can help cancers evade the immune system and why researchers are looking for ways to overcome this barrier