CAR T-Cell Therapy for Mesothelioma in New Phase I Trial

Researchers at Memorial Sloan Kettering in New York are about to try a new kind of CAR T-cell therapy for mesothelioma in human patients. 

This is the first Phase I trial of the new CAR T-cell approach. The therapy involves removing some of a patient’s T-cells, modifying them, and giving them back to fight cancer. 

The new CAR T-cell therapy for mesothelioma involves cells that have been modified in new ways. They still seek out cancer cells. But these CAR T-cells are made to last longer and to undermine a primary mesothelioma cell defense mechanism.

The FDA approved the study in September. Memorial Sloan Kettering is recruiting mesothelioma patients for it now. 

T-Cells That Target Mesothelioma Cells

CART T-cell therapy for mesothelioma is a type of immunotherapy. It starts with T-cells from the patient’s blood. Scientists alter the cells to recognize certain antigens on the surface of cancer cells. Then they give them back to the patient.

In the case of mesothelioma, the main targeted antigen is mesothelin. Mesothelioma patients tend to produce extra mesothelin. This protein helps drive the growth and spread of their cancer. People with high levels of mesothelin stand to benefit the most from CAR T-cell immunotherapy. 

The new CAR T-cell therapy for mesothelioma uses cells that are engineered to last longer before they die out. It also acts on another protein called PD-1. PD-1 helps keep the immune system from kicking into overdrive when it detects an invader. 

But when that invader is cancer, an active immune system is a good thing. Many mesothelioma patients produce extra PD-1. The new approach blocks this so that the CAR T-cells can do their job better. It is the first CAR T-cell treatment to combine long-living cells and PD-1 blocking. 

First Trial of the New CAR T-cell Therapy for Mesothelioma

Atara Bio makes the new CAR T-cell therapy for mesothelioma. They call it ATA2271. They developed the treatment in collaboration with Memorial Sloan Kettering researchers. 

The new trial will test it in mesothelioma patients for the first time. Mesothelioma patients are a critical group. They have fast-growing cancer on the lining around their lungs and few good treatment options. The FDA approved CAR T-cell treatment for people with some blood cancers. Atara Bio hopes their version will be the first to win approval for mesothelioma.

“This milestone marks an important moment in the advancement of cell and gene immunotherapy for patients, for the field, and for Atara,” says Jakob Dupont, Global Head of Research and Development at Atara Biotherapeutics.

To be in the study, pleural mesothelioma patients must have failed with other treatments.. They also cannot have tried CAR T-cell therapy for mesothelioma before. They must be healthy enough to do most of their daily activities. 

Patients will start by giving some blood. They will get a dose of a chemotherapy drug called cyclophosphamide. Then, the modified cells will go directly into the pleural space around the lungs. They are delivered through a pleural catheter. 

A Phase I trial is mainly to test safety. Future trials will test the effectiveness of the treatment and establish the best dose.

Sources:

“A Phase I Study of CAR T-Cell Immunotherapy for Pleural Mesothelioma”, Memorial Sloan Kettering website, https://www.mskcc.org/cancer-care/clinical-trials/20-328

“Atara Biotherapeutics Announces FDA Clearance of IND for ATA2271, a Next-Generation Autologous Mesothelin-Targeted CAR T with Novel PD1DNR and 1XX Technologies Combined to Treat Solid Tumors”, September 8, 2020, Alarta Bio news release, https://investors.atarabio.com/news-events/press-releases/detail/205/atara-biotherapeutics-announces-fda-clearance-of-ind-for

Mesothelin-targeted CAR T-cell Therapy in Patients With Mesothelioma, Clinical Trial website, https://clinicaltrials.gov/ct2/show/NCT04577326