Clinical trial of purified CAR-T cell therapy awarded NCI grant to expand

A clinical trial at MUSC Hollings Cancer Center that has shown success with the first two patients has now received $3.2 million in funding from the National Cancer Institute to expand.

Brian Hess, M.D., and Shikhar Mehrotra, Ph.D., have partnered on a project to develop “purified” CAR-T cells to treat people with certain B-cell non-Hodgkin lymphomas who have already tried other therapies.

CAR-T cell therapy is FDA-approved for certain types of blood cancer, but the Hollings trial is testing a new patented variation that the researchers hope will have longer-lasting results with fewer side effects.

So far, two patients have been treated through the clinical trial, and both have shown complete remission with fewer of the side effects that can come with conventional CAR-T cell therapy, like fever, low blood pressure, seizures and other effects that can lead to hospitalization in an intensive care unit.

Ted Kopacko was the first patient in the trial. He was first diagnosed with marginal zone lymphoma in 2013 and has undergone multiple treatments with standard therapies. The type of lymphoma that he has isn’t eligible for any of the FDA-approved CAR-T cell therapies, but he was eligible to participate in this clinical trial.

Kopacko, who underwent the therapy in January, said that after all of the ups and downs of treatment and recurrence over the years, the CAR-T cell therapy was remarkably anticlimactic. He didn’t have any of the side effects that usually come with this type of therapy.

 

“It’s definitely been an adventure,” he said. “To be the first person to have the purified cells – like I mentioned to Doctor Hess, ‘First time up and you guys hit one out of the park.’”

“Congratulations to Hollings,” he added. “It shows what these people are doing. They took me – and I was really struggling when I came here in November – and in a little bit over three months, they turned me around.”

It takes years to get to the point of treating patients. Mehrotra began working on this idea in his lab in 2013 and published the findings in a 2018 paper, which served as the basis for generating the CAR-T-cells, with his unique spin.

A few years ago, seed funding from Hollings enabled the team to begin planning to take the treatment to patients, and Kopacko became the first patient this year.

CAR-T cell therapy takes a patient’s own T-cells, which are part of the immune system, and engineers them in the lab to target solely on a protein that appears on the surface of cancer cells.

Mehrotra likened the process to putting eyes on the T-cells so that they could suddenly “see” the cancer. In a further refinement, his lab added a marker so that the most effective cells, now called CAR-T cells, could be isolated, and the purified product is reinfused into the patient.

By performing this process locally, the Hollings team can eliminate the need to freeze and transport the product, which reduces viability, and can lower the cost of the treatment.

The trial treatment is limited in availability at this time. Because it’s an investigational drug, patients must be spaced at least 28 days apart to allow for monitoring of potential side effects. That timeline will shorten as the trial gathers data, Hess said.

The funding from Hollings allowed for a trial of 10 patients. This month, Mehrotra and Hess received word that the National Cancer Institute awarded them a five-year $3.2 million grant, which means that 30 to 35 patients will be treated in the trial.

 

They were also honored this month by the Zucker Institute for Innovation Commercialization at MUSC, which awarded them its Technology Breakthrough Award, which recognizes an MUSC innovation that represents a significant leap forward in its field.

Hess said it’s gratifying to see how well the first patients are doing.

“As a physician, you always have some tempered optimism, but with the first patient not having any toxicity, having such a good response – that’s about as exciting as it gets.”

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