The most common form of lung cancer, called non-small cell lung cancer, affects more than 200,000 people in the US each year. Tumors from this type of lung cancer don’t often trigger an immune response, so scientists refer to them as “cold” tumors. Most current cancer treatments, such as chemotherapy and radiation, trigger the body’s immune system to help destroy cancer cells. But “cold” tumors don’t respond to these treatments.
A type of white blood cell that helps in immune responses is called a T cell. T cells that specifically target cancer cells are called tumor-infiltrating lymphocytes, or TIL for short. Scientists have extracted TIL cells from existing tumors in the body and genetically modified them by attaching proteins to the surface that can recognize and attach to cancer cells. They then inject the modified cells back into the body, in a treatment called adoptive cell therapy.
When successful, adoptive cell therapy provides the patient with a supply of T cells specially equipped to fight off cancer, reducing the likelihood of the cancer returning. Scientists have used adoptive cell therapy in previous studies to successfully treat breast and cervical cancer. However, they have not yet tested this method on lung cancer.
Another method doctors have for tackling cancer uses immunotherapy drugs. Proteins located on the surface of T cells and cancer cells can sometimes interact, camouflaging the cancer cells so the T cells no longer recognize them. Scientists have used immunotherapy drugs to block the protein on the T cell from interacting with the protein on the cancer cell, stopping this camouflage effect.
In a recent study, researchers combined adoptive cell therapy with a protein-blocking immunotherapy drug to treat lung cancer. To determine whether combining these 2 treatment methods is safe and effective, the scientists selected 20 lung cancer patients who had never received protein-blocking treatments before. Half the patients were current or former smokers. They first treated the patients with 4 cycles of protein-blocking drugs, administered every 2 weeks, and continued this method if it worked. If the tumor continued to progress, the scientists began adoptive cell therapy on the patients.
Of the 20 patients in the trial, 16 had additional tumor growth after protein-blocking treatment, so they received adoptive cell therapy as a second treatment. These patients continued to receive treatment for up to a year, depending on their response to the drug. The researchers monitored the patients’ responses to the treatment using a type of X-ray imaging, called CT scanning, to detect cancerous tumors.
The researchers found 13 of the patients who received adoptive cell therapy responded to the treatment, meaning their tumors shrunk. Two of these patients showed a complete response to the treatment, meaning there was no trace of cancerous tumors remaining in their bodies.
They also found the tumors continued to shrink in 11 patients at the 1-month check-up after treatment. The scientists measured a median decrease of about 36% in tumor diameter. Only 1 patient had an increase in tumor size, but that patient experienced no disease-related symptoms for 1.5 years post-treatment. They interpreted these results to suggest the adoptive cell therapy was successful in recognizing cancerous cells when re-administered into the patient.
The researchers noted 2 patients who were using assisted breathing machines died of underlying health conditions during the treatment. To mitigate this issue in the future, the scientists added criteria specifying that patients must have normal blood tests and a minimum level of lung and heart function in order to receive adoptive cell therapy.
Common side effects the patients experienced included nausea and diarrhea. The scientists also measured low levels of certain minerals in the blood of some patients. The team thus concluded the combination of protein-blocking drugs and adoptive cell therapy was a safe treatment with limited side effects for patients who met their criteria.
The researchers showed these combined treatments could successfully reduce tumor growth in patients with lung cancer, but acknowledged their study has limitations. They noted this specialist treatment was successful in 2 academic cancer centers, but implementing it daily in a common hospital setting could be less feasible. They also recognized their group of patients was highly specific, excluding patients with certain health complications or patients who had protein-blocking treatments before. They suggested future work should focus on improving methods used to make T cells and reducing side effects so the therapy could be applied to a broader group of people.