MUSC Health on track to offer new gene therapy for cancer

Young patients with leukemia may be able to get a new type of treatment known as CAR T-cell immunotherapy at MUSC Health in the near future, possibly within a year, according to tumor immunologists Chrystal Paulos and Juan Varela. “We’re definitely positioning ourselves to be one of the centers to offer the therapy,” Varela said.

Paulos and Varela collaborate at the Medical University of South Carolina, drawn together by their common interest in the field of adoptive T-cell transfer, or ACT. Paulos, who has been closely involved in CAR T-cell research for more than a decade, called the treatment a game changer. “I think it’s a major, exciting discovery,” Paulos said. “I’m very thrilled that it has come all the way to a recommendation by an FDA advisory committee.”

By the end of October, the Food and Drug Administration could approve the use of the “living drug” approach for kids and young adults with B-cell acute lymphoblastic leukemia who haven't responded to standard treatment or have had the cancer recur. In a clinical trial presented to the FDA, more than 80 percent of the children who got the treatment went into remission, according to the drug company Novartis.

With that in mind, Varela, a doctor specializing in treating people who have blood cancers, believes final FDA approval is likely. “It’s exciting because it’s the first T-cell-based therapy that’s going to be approved. I have been working in this field for 15 years, and it’s wonderful to finally see something coming through that we can offer patients. It’s a good time to be an immunologist.”

It may be a good time for fighting other types of cancer, too. CAR T-cell immunotherapy is being tested as a possible treatment for blood, brain, breast, gastrointestinal, lung, ovarian, pancreatic and skin cancer.

How it works

Paulos described how the treatment works. “T-cells, which play a key role in the immune system, are removed from the patient. They’re genetically altered to produce chimeric antigen receptors, CARs, or T-cell receptors, TCRs, which recognize and target proteins specifically linked to cancer.”

Varela said that genetic alteration involves the use of a retrovirus or lentivirus that is in the same family as HIV to trigger the changes. “We use the virus as a courier to take the messaging to the DNA of the cells. We take the bad stuff out of the virus and put in what we want and use the capability of the virus to deliver the material we need to deliver.”

The cells are grown in the lab until there are millions or even billions of them. Then the engineered T-cells are returned to the patient’s body, where they continue to divide and work to conquer cancer.

Since CAR-T cell treatment is so personalized, if approved, it may cost patients more than $300,000. It also comes with risks that include:

• Cytokine-release syndrome, which can cause reversible symptoms including a fever, breathing problems, delirium and seizures
• B-cell aplasia, which reduces the body’s ability to make antibodies
• Tumor lysis syndrome, which is a life-threatening condition caused by the breakdown of dying cells

But Varela said for patients with few or no other options, the treatment is a welcome new source of hope.

Paulos has a good perspective on how CAR T-cell immunotherapy got to this point. While she now runs a lab at MUSC developing new T-cell treatments for patients with advanced cancer, her resume includes postdoctoral fellowships with two tumor immunologists who are leading the way in CAR T-cell immunotherapy: Nicholas Restifo at the National Cancer Institute and Carl June at the University of Pennsylvania. “As a team, we are the driving force behind this movement,” Paulos said. "My lab has two NCI grants on how to improve this therapy."

She has plenty of immunotherapy colleagues at MUSC, too. Last week, some of them, along with Paulos, spoke to the public at a Science Cafe about this fascinating time in cancer treatment. They’re nicknamed the immunotherapy “dream team.” Science Cafes are fun, informal talks about research that often take place at Charleston Beer Works.

Immunotherapy at MUSC Health

Back on the MUSC campus, there’s an important facility that helps with the scientists’ and doctors’ work, and it's one of fewer than 20 clean cell facilities in the country. It’s a lab that can help ensure that T-cells removed from patients for treatment are unlikely to be tainted with bacteria or infection. It’s sure to stay busy. At MUSC Hollings Cancer Center, a National Cancer Institute-designated cancer center, more immunotherapy trials and treatments are underway than at any other institution in the state.

Current immunotherapy treatments offered at MUSC Health include:

• Monoclonal antibodies (aka targeted therapy), which are drugs that bind to or mark cancer cells so the immune system can find them more easily
• Cytokines, which are proteins made by the body’s cells that help the immune system fight cancer
• Vaccines, which boost the immune system’s response to cancer cells
• Bacillus Calmette-Guerin, a bacteria used to treat bladder cancer

Varela said immunotherapy is becoming the fourth pillar of cancer treatment, joining chemotherapy, radiation and surgery. “This a brand-new way to treat cancer, and in my view, this is going to be the one that’s most effective.”