Pushing immunotherapy research forward with Dr. Christian Capitini

“It’s really important to come here and see the kind of research that’s going on with your own eyes,” he said. “People really can and should feel like this is their cancer center. They’re a part of the mission just as much as we are.”

For nearly ten years, Capitini 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, N.J., to Madison, Wis.

Capitini’s interest in immunotherapy began in high school, during a chance summer internship at the Center of Molecular Medicine & Immunology in his home state of New Jersey. “It just made me so passionate about cancer immunotherapy,” he said. “From that point on, every immunotherapy opportunity I could find, I pursued it.”

After earning a degree in biology and attending medical school, he completed a residency in pediatrics at the University of Minnesota, followed by a fellowship in pediatric hematology/oncology at Johns Hopkins University and the National Cancer Institute.

He was then recruited to UW-Madison in 2011: a perfect fit and compliment to the program that Paul Sondel, MD, PhD, was building around pediatric immunotherapy. Among other achievements, Sondel was instrumental in the testing of and approval of dinutuximab, an antibody therapy aimed at treating children with high-risk neuroblastoma. The way Sondel approached and valued immunotherapy was something that 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 look at,” Capitini said. “In the case of dinutuximab, that antibody was actually incorporated into upfront therapy. It was just really nice to see it incorporated with our standard treatments, and actually show a dramatic impact on survival.”

The idea that immunotherapy could be built into the “fourth pillar” of cancer treatment, to stand alongside chemotherapy, radiation and surgery – and in some cases, replace it – was a clear goal of the program, and it didn’t take long for Capitini to jump right in.

A first-of-its-kind cell therapy

One area of particular interest for Capitini in recent years has been CAR T-cell therapy, a specific type of immunotherapy now used to treat certain hematologic cancers. During this multi-step treatment, white blood cells, or T cells, are withdrawn from a patient and sent to a lab, where they are modified with special receptors, known as chimeric antigen receptors or CARs. These new “supercharged” CAR T-cells are later infused back into a patient, and are essentially programmed to bind to cancer cells and destroy them.

With Capitini at the helm, UW participated in the first multi-center CAR T clinical trials ever developed. These phase II trials – which were also the first CAR T studies in the state of Wisconsin – looked at the effectiveness of a specific therapy, known as tisagenlecleucel, in treating children with relapsed or refractory B-cell leukemia.

The treatment was approved by the FDA in 2017 – thanks partially to testing at UW Carbone – and became the first gene therapy ever approved by the agency. Other types of CAR T-cell therapy would soon follow, including a similar version to treat adult patients, which bucked a conventional trend in pediatric cancer research.

“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 said. “Dinutuximab and tisagenlecleucel really 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 also underway to determine if CAR T-cell therapy can be effectively used sooner in the treatment process. Like many other immunotherapies, the CAR T approach is typically only used when a patient stops responding to other, more traditional treatments.
But another clinical trial lead by Capitini is offering the therapy earlier to some patients identified as having a high-risk of future cancer recurrence. “If we can get positive results from that, it would suggest that we can potentially move a lot of these exciting therapies into the upfront setting,” he said. “More importantly, we could also the remove toxic chemotherapies that often have long-term, toxic side effects,”

Later this year, Capitini will also oversee UW Carbone’s first-ever clinical trial using CAR T-cell therapy in patients with solid tumors. That’s important, because while immunotherapy has made great strides in treating pediatric patients with hematologic malignancies, Capitini notes that less progress has been made when it comes to solid-tumor cancers.

The study will specifically target children with osteosarcoma, the most common pediatric bone cancer. If the trial is successful, it could potentially 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 recognition both locally and nationally.

Along with other physician-scientists from UW Carbone, he was named as one of the original members of the pediatric cancer Dream Team in 2013. A collaboration between the St. Baldrick’s Foundation and Stand Up to Cancer, the 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 were recognized with a Team Science award from the Society for Immunotherapy of Cancer – an honor only bestowed upon institutions who have significantly advanced the field over the past three decades.

“It’s a tremendous honor, especially to be on the list with such other prominent cancer programs,” Capitini said. “It really reflects the fact that it’s a team effort here. I’m working on just one piece of a very large puzzle, where people who have non-overlapping areas of expertise come together for a common problem.”

Back at UW Carbone, Capitini was recently named as the co-leader of the center’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.

They are lofty goals, but Capitini believes the key to success involves bringing researchers together across campus to forge new and unique collaborations. A perfect example of that is his own recent collaboration with Krishanu Saha, PhD, an associate professor of biomedical engineering at UW 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 than how the current clinical products are made,” he said. “We hope that that’ll bring down the cost, and we also hope it’ll improve the quality of the product.”

At the end of the day, it’s those collaborations and relationships that keep bringing Capitini back day after day, and why he continues to call UW home.

“There’s no secret that it’s the people that make this place special,” he said. “You can really feel a shared mission here to move the field forward.”

This article first appeared in Quarterly Magazine, the official magazine for alumni, friends, faculty and students of the University of Wisconsin School of Medicine and Public Health.