Curated Cancer Care

Carolina researchers are using CAR-T cells to create better and personalized cancer treatments in one of the largest cell therapy facilities on the East Coast.

February 26th, 2024

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When you ask Gianpietro Dotti and Barbara Savoldo when they first met, both pause and smile.

“A very long time ago,” Dotti says.

“We met in Italy. I was doing my fellowship, and he was working in the lab — and I guess we both had a common passion and that’s how it happened,” Savoldo shares, laughing. “We had the same interests and then developed the same goals.”

The goals? To find better treatments for cancer and, eventually, other diseases.

The husband-and-wife team joined the UNC Lineberger Comprehensive Cancer Center in 2015 to start its good manufacturing practice (GMP) facility, monitored by the FDA. Often called a “clean facility,” the GMP uses an advanced air filtration system and requires researchers to wear head-to-toe PPE. These measures maintain a sterile space where treatments can be produced with minimal risk of contamination from bacteria or disease.

Creating a CAR-T therapy pipeline

Carolina’s facility supports cell therapies created in campus labs by scaling up the production to millions of cells, which can then be infused in patients at UNC Hospitals. With their combined expertise in oncology, cell biology, and immunology, Savoldo and Dotti oversee the university’s CAR-T therapy program.

Developed in 2010 by clinical researchers at the University of Pennsylvania, the therapy has been successful at treating blood cancers like leukemia, lymphoma, and myeloma. Thanks to a handful of FDA-approved treatments, about 40% of patients with aggressive forms of these diseases have experienced remission.

There are currently 10 adult and pediatric CAR-T therapy phase I clinical trials in progress at UNC-Chapel Hill’s GMP facility. These include patients with blood cancers and solid tumor cancers like ovarian, lung, and glioblastoma.

CAR-T therapy consists of genetically engineered antibodies and T-cells that are combined to make a super-cell to fight cancer. Antibodies remove anything not recognized by the immune system, like bacteria and viruses, and T-cells are white blood cells that do the elimination themselves. Using blood samples from a patient, Dotti and Savoldo’s research team can isolate their T-cells and reprogram them to express an antibody to attack their specific cancer.

“It seems like fiction science, but it’s not,” Dotti says. “CAR-T cells can recognize targets and kill them.”

Once the lab experiments on campus prove successful, the cells get moved to the GMP facility, where the researchers can produce millions of them over several weeks. Then, they’re cryogenically frozen and stored for a long time. When the patient is ready to receive the treatment, the CAR-T cells are shipped to UNC Hospitals and reinfused in their body to target their tumor.

“You want to have an army of cells for a patient so they can treat and take care of cancer right away,” Savoldo says.

Being able to replicate cells en masse is a big deal, according to Savoldo. Oftentimes, labs will outsource this work to private companies. UNC-Chapel Hill’s cell therapy pipeline — from small experiments in the lab to large-scale cell production at the GMP facility to infusion in patients participating in clinical trials — saves the university money and time and streamlines translational science.

While CAR-T therapy has gained recent attention from the FDA upon reports that it may increase a person’s risk of cancer, Savoldo stresses that every medication has side effects. And there are other factors to consider. Patients enrolled in these clinical trials already have a predisposition to cancer, their cancers have not responded to other therapies, and many have weakened immune systems from years of chemotherapy, radiation, and other treatments.

“We have to be vigilant,” she says. “This is why we track patients for 15 years after receiving the therapy.”

The risk is often worth the reward. Nearly 150 patients have participated in CAR-T clinical trials at UNC-Chapel Hill. While it’s hard to track disease reduction for phase I clinical trials, which focus on safety, about 60% of patients who participated in the facility’s clinical trial for Hodgkin’s lymphoma are now in remission.

“The remission rate is even better with the new trial we are conducting,” Savoldo shares. “In addition to the CAR-T cells, we have included a molecule that helps T-cells traffic to the tumor site. Some people don’t have other options for treatment, so this has been remarkable.”

Collaborating to advance cancer care

This success, in part, comes from Dotti and Savoldo’s complementary skill sets — and is why they were hired by the university. They have nearly two decades of experience using cell therapies to treat patients with cancer.

Savoldo focuses on cell function and improving how they attack cancer tumors, which guides Dotti’s work in modifying these cells. He specializes in immunology and studies how to improve the immune system.

“Gianpietro has all this important background knowledge about viruses and vectors,” Savoldo says. “This is what we use for manipulating the cells so that they can recognize the tumor. This is a difficult job because you have to do it safely. You have to make sure everything is perfect and done in the way that is safest for the patient.”

Savoldo also oversees the lab to clinical trial pipeline.

“Barbara is a little bit what they call ‘the glue.’ She’s connected with the clinicians and the GMP facility directly, and she supervises what’s going on with these cells,” Dotti says. “Then she comes back to me to discuss issues and find solutions.”

In addition to running the facility, Dotti and Savoldo started the Sonia Savoldo GBM Fund at UNC Lineberger to advance immunotherapy research for an aggressive, fast-growing brain cancer called glioblastoma (GBM). The fund also provides financial support to patients and their families, who often spend weeks, or even months, away from home to access costly care.

Dotti and Savoldo want to reduce this burden. They began the fund in 2019, when Savoldo’s youngest sister, Sonia, received a glioblastoma diagnosis. This motivated them to create a clinical trial for the disease at Carolina, but Sonia passed away in 2022 before it started.

“Sonia was genuinely excited that we were working on developing a therapy for people like her,” Savoldo says. “Opening the CAR-T cells clinical trial for patients with GBM at UNC was a significant accomplishment. While it sometimes evokes painful memories, being involved in this trial connects me to these patients and their families, motivating me to do more.”

Gianpietro Dotti is co-leader of the UNC Lineberger Immunology Research Program and a professor in the Department of Microbiology and Immunology within the UNC School of Medicine.

Barbara Savoldo is co-leader of the UNC Lineberger Immunology Research Program and the Champion Mitchell Distinguished Professor in the Department of Pediatric Hematology/Oncology within the UNC School of Medicine.

This research is made possible with support from the University Cancer Research Fund, a landmark investment from the state of North Carolina created by the N.C. General Assembly to support cancer research.