CAR T-cell therapy for lung cancer

The good news

Jalal Ahmed MD, PhD, an Assistant Professor at the Precision Immunology Institute, Department of Radiation Oncology, Icahn School of Medicine, Mount Sinai in New York City, has published an important paper entitled “Targeting the tumor microenvironment to advance CAR-T cell therapy for lung cancer” in the journal, Nature Cancer. Dr. Ahmed’s work was supported by a grant from the Lung Cancer Research Foundation (LCRF) that he received in 2018.

Why it’s important

CAR (Chimeric Antigen Receptor) T-cell therapy is a form of immunotherapy. T cells are white blood cells in the immune system that have receptors on their surface that can recognize cells that contain abnormalities called antigens, i.e. cancer cells. The T cells become activated and proceed to kill the abnormal cells. CAR T-cells are the patient’s own immune cells, reprogrammed in a lab to act like guided missiles that are trained to seek out and attack cancer cells specifically. These T cells are returned to the patient, and they detect and kill the cancer cells. CAR T-cells can also continue to multiply in the bloodstream so that they act like a “living drug.”

CAR T-cell therapy is currently approved for the treatment of several blood cancers. This type of immunotherapy has been attempted in many other cancers but unfortunately has not been successful. There are many explanations as to why this therapy has not been as effective in the treatment of other malignancies such as lung cancer. The issues are very complicated, and scientists have gone back to the laboratory to get a better understanding of the biology involved in the use of T-cell therapy.

Dr. Ahmed focused his research on the tumor microenvironment where certain components can suppress the immune response. By using a novel mouse model, he was able to demonstrate that incorporation of radiation dramatically increased the activity and persistence of the CAR T-cells. Sustaining CAR T-cell activity has been a major challenge. Dr. Ahmed found that the persistence of the CAR T-cells depended on dendritic cells which are immune cells that present the antigens to the T cells thus initiating the immune response. These findings establish a critical mechanism through which dendritic cells maintain the CAR T-cell pool in irradiated tumors, thus supporting translation of this approach to advance CAR T-cell therapy for solid tumors.

What it means for patients

This research is important for patients because by understanding the interactions of the immune system, scientists and physicians can use this information to design more effective therapy in the CAR T-cell space. It is difficult to tell how soon the results of Dr. Ahmed’s research will be used in a clinical trial but clearly this represents progress. It is hoped that CAR T-cell therapy will be as effective in the treatment of lung cancer as it is in blood cancers. It is important to note that any progress in lung cancer may be applied to the treatment of other malignancies.

What to look for

There is a great deal of research going on in the use of CAR T-cell therapy. The efforts in basic science help to improve our understanding of the immune system and subsequently these scientific breakthroughs are translated into clinical trials for patients. This is a very exciting field of research, and many advances are anticipated in the future. LCRF is thrilled that this research was made possible because of an LCRF grant. Our scientific review process ensures that we support the best innovative research. LCRF will continue to make it our mission to fund research that will ultimately lead to a cure for lung cancer.

More to come!