CAR-T Cells + Keytruda: New Immunotherapy for Pleural Mesothelioma?

Researchers at a top US cancer center are experimenting with a new approach to immunotherapy for pleural mesothelioma – with exciting results. 

The research was done at Memorial Sloan Kettering Cancer Center in New York and published in a recent issue of Cancer Discovery. 

The Phase I trial is the first to treat pleural mesothelioma patients with CAR-T cell therapy and the PD-1 blocker pembrolizumab (Keytruda). Although the trial was small, 83 percent of patients lived for more than a year. Some lived for nearly two. 

Malignant Mesothelioma commonly claims the lives of patients within months. This new type of immunotherapy for pleural mesothelioma could be a breakthrough in improving survival.

The Challenge of Malignant Mesothelioma

Scientists have known about mesothelioma, the so-called “asbestos cancer”, since as early as the 1940s. That is when asbestos workers started to come down with a mysterious lung disease.

But even after decades of research, there is still no cure for mesothelioma. Doctors have tried many types of treatments. But chemotherapy and radiation only stop progression for a while. Immunotherapy for pleural mesothelioma seems to hold the most promise. 

Immunotherapy refers to any manipulation of the immune system to treat disease. There are many types of immunotherapy. Some types of immunotherapy for pleural mesothelioma have been more effective than others.  

The new study suggests that CAR-T cells and Keytruda may be a powerful weapon against this tenacious cancer.

How Does This Immunotherapy for Pleural Mesothelioma Work?

T-cells are a type of immune system cell. CAR-T cell therapy involves removing some of these cells from the patient’s body. The cells are changed in the laboratory so that they will attack cancer cells. 

In immunotherapy for pleural mesothelioma, scientists change the T-cells to find and attack cells that express mesothelin. Mesothelin is a protein on the surface of mesothelioma cells. 

But there is a problem. Pleural mesothelioma cells also express another protein that helps repel T-cell attacks. This protein is called PD-1. Keytruda (pembrolizumab) can disable this protective mechanism by blocking PD-1.

A One-Two Punch for Mesothelioma

The researchers at Memorial Sloan Kettering combined CAR-T cell therapy with Keytruda for a one-two punch. In this immunotherapy for pleural mesothelioma, the programmed T-cells find and attack mesothelioma cells and the Keytruda prevents them from protecting themselves. 

Researchers delivered CAR-T cells into the pleura of 25 pleural mesothelioma patients. Eighteen of those patients also received Keytruda. 

“Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%),” reports lead author Prasad Adusumilli. “Stable disease was sustained for (greater than or equal to) 6 months in 8 patients.”

Two of the patients on this immunotherapy for pleural mesothelioma had “complete metabolic response” according to their PET scans. The treatment also appeared to be “safe and well-tolerated.” The research team concludes that the combination is promising enough to warrant further study. 

Source:

Adusumilli, P, et al, “A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab”, July 15, 2021, Cancer Discovery, Online ahead of print, https://cancerdiscovery.aacrjournals.org/content/early/2021/07/15/2159-8290.CD-21-0407