CAR-T Cell Therapy with PD-1 Immunotherapy Extends Survival in Pleural Mesothelioma

CAR-T Cell Therapy for Mesothelioma

CAR-T cell therapy is a growing area of research for all cancers, including mesothelioma. This form of immunotherapy works by injecting the body with engineered immune cells that can recognize specific proteins on cancer cells and attack. The U.S. Food & Drug Administration (FDA) has already approved this treatment for several cancers like lymphoma, and it continues to be tested in mesothelioma clinical trials.

Most recently, a phase 1 clinical trial testing CAR-T cell therapy targeting mesothelin in combination with PD-1 inhibitors has shown success in achieving stable disease and extending survival for pleural mesothelioma patients.

Testing CAR-T Cell Therapy with PD-1 Inhibitors

T cells are white blood cells that help protect the body against disease. CAR-T cell therapy works by ensuring T cells can still recognize the cancer cells in the body, as many have been able to trick the immune system into thinking they are normal, healthy cells. Researchers have been experimenting with genetically modified T cells to be injected into a patient’s body with the ability to target specific proteins on cancer cells.

In past studies, researchers have identified that mesothelin, a glycoprotein that naturally has very low levels in the linings of organs, overexpresses in certain cancers like mesothelioma. In such cases, it could be the perfect target for the modified T cells to attack.

Another type of immunotherapy, called PD-1 inhibitors, have also been widely studied for mesothelioma. Like with CAR-T cell therapy, this form of immunotherapy works by blocking the signal between PD-1 (a protein found in both normal and cancer cells) and the PD-L1 protein on mesothelioma cancer cells. By blocking the signal, T cells can recognize the mesothelioma cells and attack.

This recent phase 1 clinical trial was designed to see how the CAR-T cell therapy targeting mesothelin would work with a PD-1 checkpoint inhibitor.

Combination Therapy Helps Some Achieve Stable Disease

The clinical trial included 18 malignant pleural mesothelioma patients, one lung cancer patient and one breast cancer patient, all of whom showed a high expression of mesothelin. The participants were first treated with cyclophosphamide, a chemotherapy drug. Doctors then intrapleurally administered the engineered CAR-T cells through either a pleural catheter or an interventional radiology procedure. Through these measures, the immunotherapy was applied directly into the pleural cavity, rather than throughout the body as with many other systemic treatments.

Afterward, 14 of the patients were also administered with a PD-1 checkpoint inhibitor. Doctors treated the patients with an escalating scale of doses, monitoring any treatment side effects and the impact on the patients’ cancer.

By January 2019, when the researchers cut off the data, the patients had been monitored anywhere from 13 to 77 weeks, with a median follow-up of 31 weeks. At this point, researchers noted many positive results. Of the 14 mesothelioma patients treated with the combination immunotherapy, five patients achieved partial responses and four were considered to have stable disease. This means the cancer didn’t grow or spread during treatment.

Two patients within the study were even considered to achieve complete response, meaning no active cancer could be detected. In their most recent update, the principal investigator explained one of these patients survived for 16 months with minimal treatment, after initially facing a prognosis of about six months. The patient passed from complications not related to his cancer.

The second patient who achieved complete response is currently at 14 months survival with no signs of recurrence.

Further Research Ahead

The positive results from the clinical trial provide the researchers and the larger mesothelioma community with hope for this treatment. While further study is needed to better understand any long-term effects of the treatment, as well as test different immunotherapy drug combinations, the early results are promising.

Pleural mesothelioma patients typically survive one year when treated with standard options like chemotherapy, depending on other factors like stage at diagnosis. Immunotherapy has helped extend survival for many patients, particularly Keytruda®. Immunotherapies have become more widely recommended as a standard treatment for mesothelioma, even outside of clinical trials, because of their success.

Researchers hope with the next phases of this clinical trial they will continue to see more positive results, as well as take steps to finding a mesothelioma cure.