Among the first things Christian Capitini, MD, wants to do once the COVID-19 pandemic is over is welcome visitors to his laboratory. “It’s really important to come here and see, with your own eyes, the kind of research that’s going on. People can and should feel like this is their cancer center. They’re a part of the mission just as much as we are,” says Capitini, an associate professor in the Department of Pediatrics at the University of Wisconsin School of Medicine and Public Health (SMPH).
For nearly 10 years, he has maintained an active research lab at the UW Carbone Cancer Center while also providing care for children with cancer at the American Family Children’s Hospital. It’s a varied mix of clinical and laboratory responsibilities, but there’s one big thread that ties it all together: immunotherapy.
While the idea of using the body’s own immune system to fight disease isn’t new, significant advances made at UW-Madison over the past decade have transformed immunotherapy into an increasingly viable treatment option, especially in pediatrics. And there’s plenty on the docket in 2021 and beyond to push immunotherapy even further. So, it’s no wonder why Capitini is eager to get back to welcoming the public into his lab for a friendly tour.
From Madison, New Jersey, to Madison, Wisconsin
Capitini’s interest in immunotherapy began in high school, during a chance summer internship at the Center for Molecular Medicine and Immunology in his home state of New Jersey.
“It made me so passionate about cancer immunotherapy,” he recalls. “From that point on, I pursued every immunotherapy-related opportunity I could find.”
After completing a bachelor of arts in biology with honors at Drew University in Madison, New Jersey, Capitini went on to earn his medical degree with distinction in research honors from the University of Rochester School of Medicine and Dentistry in New York. He also completed a residency in pediatrics at the University of Minnesota in Minneapolis and a fellowship in pediatric hematology/oncology at Johns Hopkins University and the National Cancer Institute in Baltimore and Bethesda, Maryland, respectively.
In 2011, Capitini was recruited to the SMPH—which he considered a perfect fit due to the program Paul Sondel, MD, PhD ’75 (PG ’80), was building around pediatric immunotherapy. Among other achievements, Sondel was instrumental in the testing and approval of dinutuximab, an antibody therapy aimed at treating children with high-risk neuroblastoma. The way Sondel approached and valued immunotherapy immediately appealed to Capitini.
“Most immunotherapies are developed as kind of a last-ditch treatment for patients who have failed all other options and have nothing left to consider,” Capitini explains. “In the case of dinutuximab, that antibody was incorporated into up-front therapy. It was really nice to see it incorporated with our standard treatments, and to watch it dramatically impact survival.”
The idea that immunotherapy could be built into the “fourth pillar” of cancer treatment, to stand alongside—and in some cases, replace—chemotherapy, radiation and surgery was a clear goal of the program, and Capitini quickly jumped in.
A first-of-its-kind cell therapy
In recent years, Capitini has been particularly interested in CAR T-cell therapy, a type of immunotherapy used to treat certain hematologic cancers. During this multistep treatment, white blood cells, or T-cells, are withdrawn from a patient and modified with special receptors, known as chimeric antigen receptors or CARs. These new “supercharged” CAR T-cells are infused back into the patient so they can bind to cancer cells and destroy them.
With Capitini at the helm, UW Carbone participated in the first multicenter CAR T clinical trials. These phase II trials—which also were the first CAR T studies in Wisconsin—looked at the effectiveness of a specific therapy, known as tisagenlecleucel, in treating children with relapsed or refractory B-cell leukemia.
Thanks partially to testing at UW Carbone, the treatment was approved by the U.S. Food and Drug Administration in 2017; it was the first gene therapy approved by the agency. Soon to follow were other types of CAR T-cell therapy, including a similar version to treat adult patients.
“Most often, a new treatment is approved in adult cancer and then, if we’re lucky, it gets tested in children and re-purposed,” Capitini notes. “But dinutuximab and tisagenlecleucel showed that while pediatric cancers may be rare, we can study them and take what we’ve learned to potentially treat more common cancers in adults.”
More research is underway to determine whether CAR T-cell therapy can be effectively used sooner in the treatment process. Like many immunotherapies, the CAR T approach is typically used only when a patient stops responding to more traditional treatments. But another multicenter clinical trial led locally by Capitini is offering the therapy earlier to some patients who have a high risk of cancer recurrence.
“If that trial shows positive results, it would suggest that we can potentially move many of these exciting therapies into the up-front setting,” he says. “More importantly, we could eliminate the use of chemotherapies that often have long-term, toxic side effects.”
Later in 2021, Capitini will oversee UW Carbone’s first multicenter clinical trial using CAR T-cell therapy in patients with solid tumors. He says this is important because while immunotherapy has made great strides in treating pediatric patients with hematologic malignancies, less progress has been made with solid-tumor cancers.
The study will target children with osteosarcoma, the most common bone cancer in children, and neuroblastoma, the most common pediatric solid tumor outside of the brain. If successful, the trial could pave the way for CAR T-cell therapy to be used as a treatment for many other types of cancer.
Dream Team and beyond
Capitini’s immunotherapy work has received local and national recognition.
Along with other UW Carbone physician-scientists, he was named as an original member of the pediatric cancer Dream Team in 2013. A collaboration between the St. Baldrick’s Foundation and Stand Up to Cancer, the nationally recognized Dream Team brings together experts in genomics and immunotherapy from different institutions—and provides much-needed funding—to find cures for difficult-to-treat childhood cancers.
More recently, Capitini and other UW Carbone immunotherapy researchers received a Team Science Award from the Society for Immunotherapy of Cancer (SITC), an honor bestowed only upon institutions that have significantly advanced the field over the past three decades.
“It’s a tremendous honor to be on the list with such other prominent cancer programs,” notes Capitini, who was elected an at-large director of the SITC in January 2021. “It really reflects the fact that it’s a team effort here. I’m working on just one piece of a very large puzzle, with people who have non-overlapping areas of expertise and come together for a common problem.”
In May 2020, Capitini was named as the co-leader of the UW Carbone’s Developmental Therapeutics Program, which is aimed at improving cancer patient outcomes by discovering new targets for cancer therapy, developing therapeutic agents and biomarkers, and translating this research into early-phase clinical trials.
These are lofty goals, but Capitini believes the key to success involves bringing together researchers from throughout campus to forge new, unique collaborations. A perfect example is his recent collaboration with Krishanu Saha, PhD, an associate professor of biomedical engineering in the UW College of Engineering and an expert on the gene-editing technology CRISPR.
“Together, we’re trying to design CAR T-cells using CRISPR Cas9, which is very different from how the current clinical products are made,” Capitini explains. “We hope that will bring down the cost and improve the product’s quality.”
This type of collaboration and relationship keeps bringing Capitini back day after day, and it’s why he calls UW-Madison home.
“There’s no secret—it’s the people that make this place special,” he concludes. “You can really feel a shared mission here to move the field forward.”
By Chris Malina
This article appears in Quarterly magazine.