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Immunotherapy to the Rescue:
CAR T-Cell Therapy Shows Promise For Mesothelioma Patients

Study Results Offer New Hope

Immunotherapy: it’s a type of mesothelioma treatment that turns the immune system into a cancer-fighting machine. And according to researchers at Memorial Sloan Kettering Cancer Center (MSK), it appears to be working.

Dr. Prasad S. Adusumilli is the lead author on a Phase 1 clinical trial using chimeric antigen receptor (CAR) T-cell therapy to attack pleural mesothelioma tumors. The patient’s T-cells, a specific type of white blood cell, are genetically engineered in a laboratory, then injected directly into the chest cavity.

Once inside the body, these reprogrammed T-cells attack a surface protein called mesothelin, which is found on cancer cells of patients with chest cavity diseases like mesothelioma.

After more than four years of work, Dr. Adusumilli’s research team has good news: specific combinations of CAR T-cell therapy shrunk the tumors — without any toxic side effects.

The Process

The clinical trial began in 2015 and followed 21 people: 19 with malignant pleural mesothelioma, one with metastatic breast cancer, and one with metastatic lung cancer. Researchers injected each patient with a single dose of CAR T-cells. Some patients also received a drug to block an additional cell-surface protein called PD-1, which prevents the immune system from attacking cancer cells.

To measure results, researchers tracked levels of CAR T-cells in the blood. They also used a mesothelin-related blood tumor marker and imaging scans to determine tumor growth or regression.

In 13 patients, mesothelioma tumors shrunk significantly. Two of them experienced a complete metabolic response, a medical term that refers to the absence of all cancer cells, or “no evidence of disease.” One patient had curative-intent surgery after the CAR T-cell treatment.

According to the study findings, the longer CAR T-cells remained in the blood, the better the therapy appeared to work.

The anti-PD1 drug also played a significant role. This medication was designed to help extend the life of CAR T-cells, which can be severely limited by solid tumors, or diseases with a heavy tumor burden, like pleural mesothelioma.

As a precaution, Dr. Adusumilli and his team of researchers engineered a “suicide” switch, or kill switch, which could be activated to kill all CAR T-cells in the event of extreme toxicity. Fortunately, it wasn’t necessary. Of the 21 patients who received the injection, not one exhibited signs of the severe toxicities that are related to this treatment.

Engineering Success

Dr. Adumusilli presented these findings at the American Association for Cancer Research (AACR) Annual Meeting, which took place on March 31st. He is cautiously optimistic.

“This is a Phase I trial,” he said. “The long-term effectiveness of this approach hasn’t been established. However, this study represents the first step toward harnessing these powerful treatment options for patients with diseases that are difficult to treat.”

Until recently, CAR T-cell therapy was only used for blood cancers like lymphoma or leukemia. The results of this study mark the first successful data set involving the treatment of solid tumors with this type of immunotherapy.

Memorial Sloan Kettering Cancer Center plans to advance the study later this year and is working on a new clinical trial for 2020.

Learn more about immunotherapy for mesothelioma treatment

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