CAR T Cells Show Strength Against Mesothelioma and Other Cancers

Therapy based on CAR T cells may prove helpful not only to mesothelioma patients but also to patients with other types of cancers.

Research involving the use of CAR T cells has been underway for quite some time now at Memorial Sloan Kettering Cancer Center in New York City. Scientists involved in the project recently disclosed some intriguing developments.

T cells are good guys. They are produced by the body’s immune system and are born to hunt invaders. They would love to hunt and kill cancer cells, if only they could find them.

T-cells have difficulty finding cancer cells because the cancer cells do a good job of camouflaging themselves. The Memorial Sloan Kettering team has been working to overcome this advantage cancer cells have.

Writing in the online journal Cancer Discovery, they said they used successfully targeted antigen CD19 in patients who were suffering from “refractory hematologic malignancies.”

The researchers explained that this means solid tumors other than mesothelioma could be targeted, too, using T-cell engineering strategies.

Mesothelioma Slowed by CAR T Cells

“Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors” was written by Memorial Sloan Kettering investigators from its Center for Cell Engineering and Department of Surgery.

CAR stands for chimeric antigen receptors. These are lab-engineered receptors that target friendly T cells. In so doing they deliver cell-surface antigens and boost the power of T cells to kill cancer cells.

The focus of this particular research effort at Memorial Sloan Kettering is mesothelin. Mesothelin is described by the researchers as a cell-surface antigen involved in tumor invasion.

It happens that mesothelin is highly expressed in mesothelioma. Mesothelin also turns out to be highly expressed in lung cancer and cancers of the pancreas, breast and ovaries, plus a number of others.

The researchers wrote that they were encouraged by the findings of a recent early-phase CAR T clinical trial they conducted to explore active immunization, or immunoconjugates, in mesothelioma patients.

This trial revealed that mesothelioma patients — as well as those with adenocarcinoma — could experience response to CAR T cell therapy without suffering toxicity.

The researchers said the clinical trial findings and earlier experimentation with preclinical CAR therapy models using either systemic or regional T-cell delivery “argue favorably for mesothelin CAR therapy in multiple solid tumors.”

Driving CARs Straight to Mesothelioma

The earlier experimentation with CAR T cells was the subject of a Science Translational Medicine journal article last year.

Testing the CAR strategy in mice only, the researchers were able to achieve impressive — and promising — results despite facing several hurdles.

One such hurdle involved figuring out how to induce large numbers of CAR T cells to attack the mesothelioma cells. A massive assault was needed in order to hit the cancer hard and for as long as possible.

They wanted it and they got it. The way they engineered those CAR T cells ensured a huge attack would occur. Basically, what they did was endow the CAR T cells with a powerful affinity for mesothelin cells.

Equally valuable was a technique the researchers developed to parachute CAR T cells directly into the battle zone. As a result, the CAR T cells arrived at the targeted mesothelin cells in undiluted numbers.

Much to the researchers’ delight, the attacking CAR T cells kept up their assault on the tumor cells for an incredible 200 days straight. Never once in that time did they let up in dishing out their punishment.

On top of that, the CAR T cells carried out attacks on tumor cells encountered some distances away from the drop zone.

Today, the researchers indicate they will continue their work with CAR T cells. They are looking for even more encouraging results in the months and years ahead.