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Husband and wife oversee Carolina’s CAR-T therapy

Drs. Gianpietro Dotti and Barbara Savoldo personalize cancer treatments in one of the East Coast’s largest cell therapy facilities.

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ٰ.  and ٰ.  met in Italy, when she was on a fellowship and he was working in a lab. They shared a common passion and developed the same goals: to find better treatments for cancer and, eventually, other diseases.

The husband-and-wife team joined the  in 2015 to start a “clean facility,” monitored by the Food and Drug Administration, where treatments can be produced with minimal risk of contamination from bacteria or disease. With their combined expertise in oncology, cell biology and immunology, Savoldo and Dotti oversee the University’s chimeric antigen receptor T-cell therapy program.

Creating a CAR-T therapy pipeline

Developed in 2010 by clinical researchers at the University of Pennsylvania, CAR-T therapy has been successful at treating blood cancers like leukemia, lymphoma and myeloma. About  with aggressive forms of these diseases have experienced remission. Clinical trials at Carolina’s facility include patients with blood cancers and solid tumor cancers like ovarian, lung and glioblastoma.

CAR-T therapy combines genetically engineered antibodies and T-cells 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.”

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 ۰ͼ Hospitals.

“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, Savoldo says. Labs often outsource this work to private companies. ۰ͼ-Chapel Hill’s cell therapy pipeline saves the University money and time and streamlines translational science.

Nearly 150 patients have participated in CAR-T clinical trials at ۰ͼ-Chapel Hill. While it’s hard to track disease reduction for phase I clinical trials, which focus on safety, about 60% of patients who took part 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.

In addition to running the facility, Dotti and Savoldo  at ۰ͼ Lineberger to advance immunotherapy research for an aggressive, fast-growing brain cancer called glioblastoma. The fund is named for Savoldo’s youngest sister, diagnosed with the disease in 2019. It also provides financial support to patients and their families. Sonia passed away in 2022 before the clinical trial started.

“While it sometimes evokes painful memories, being involved in this trial connects me to these patients and their families, motivating me to do more,” Savoldo says.