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New Immunotherapy for Mesothelioma Relies on Altered T-Cells

19103717_Immune SystemAn emerging type of mesothelioma therapy that uses altered T-cells to attack tumors is generating some excitement among researchers at Memorial Sloan Kettering Cancer Center in New York.

The approach, called CAR T-cell therapy, produces what the National Cancer Institute has called a “living drug” for targeted mesothelioma treatment.

A new review of this immunotherapy approach has some encouraging news for mesothelioma patients and their families.

Producing a “Living Drug” for Mesothelioma Therapy

CAR T-cell therapy for mesothelioma and other cancers starts by extracting some immune system cells called T-cells from a sample of the patient’s blood.

The T-cells are then altered in the laboratory using chimeric antigen receptors (CARs), which essentially program them to recognize certain antigens on the surface of cancer cells.

In the case of mesothelioma, the targeted antigen is mesothelin, a protein that is highly expressed on the surface of mesothelioma cells as well as lung, pancreatic, breast, ovarian, and other cancer cells.

How This Targeted Mesothelioma Treatment Works

CAR T-cell therapy is considered a form of immunotherapy for mesothelioma because it harnesses the power of a person’s own immune system.

Mesothelioma and other cancers are often able to slip “under the radar” and avoid immune system attack by producing certain protective proteins. But CAR T-cell therapy is designed to undermine that defense mechanism and turn the power of the immune system against mesothelioma tumors.

When the altered CAR T-cells come in contact with mesothelin-expressing mesothelioma cells, they not only attack, but they prompt the body to produce more mesothelin-attracted T-cells to help.

Proximity to Mesothelioma Tumors May Impact Effectiveness

The Memorial Sloan Kettering research team is leading the way in this form of immunotherapy for mesothelioma. In 2014, the group demonstrated that CAR T-cells work even better against mesothelioma tumors when they are delivered directly into the pleural space.

In contrast, when the team delivered CAR-T-cells intravenously into mice with mesothelioma tumors, they were unable to achieve the same level of activation or tumor eradication and the CAR T-cells did not stay in the tumors as long.

Just as importantly, this immunotherapy for mesothelioma has been shown in preclinical tests to produce few serious side effects.

“Altogether, these findings and preclinical CAR therapy models using either systemic or regional T-cell delivery argue favorably for mesothelin CAR therapy in multiple solid tumors,” writes corresponding author Dr. Prasad Adusumilli of the Center for Cell Engineering at Memorial Sloan Kettering.

The new report appears in a recent issue of Cancer Discovery.


Morello, A, et al, “Mesothelin-Targeted CARs: Driving T-Cells to Solid Tumors”, October 26, 2015, Cancer Discovery, Epub ahead of print

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