Years of hard work are sandwiched between where Paul Sondel, MD, PhD ’75, is today and his humble beginnings in the medical field – washing test tubes.
This fall, more than 800 former pediatric cancer patients who received care at the American Family Children’s Hospital and University of Wisconsin Carbone Cancer Center and their family members attended the Kids with Courage survivors’ reunion. They were hopeful as Sondel and others described recent advances in immunotherapy, which can target cancer cells without harming healthy tissue.
Despite Sondel’s extensive background in genetics and tumor immunology, as well as his multifaceted title – the Reed and Carolee Walker Professor in Pediatric Oncology at the UW School of Medicine and Public Health, head of the Division of Pediatric Hematology, Oncology and Bone Marrow Transplantation and member of the Carbone Cancer Center – he can explain in very simple terms the complex work he and his team do with immunotherapy, so patients and families can easily envision the process.
Simply stated, in the past five years, the team’s research has contributed to dramatic change in the treatment for neuroblastoma, and, in turn, the survival rate for children with this high-risk disease. With other treatments, before immunotherapy was possible, these children faced a 40 percent chance of survival. Immunotherapy treatment has boosted the survival rate to 60 percent.
Sondel’s team discovered that giving monoclonal antibodies that bind to neuroblastoma will attract white blood cells to the tumor and destroy cancer cells that remain after the traditional treatments of surgery, radiation and chemotherapy. The white blood cells are stimulated with activators, including interleukin 2 (IL-2).
These achievements with immunotherapy have attracted national attention. The highly regarded organizations Stand Up to Cancer and the St. Baldrick’s Foundation have named Sondel’s team to join six others in order to form the only pediatric cancer “Dream Team” in North America.
“The other six pediatric oncology research teams are located at the National Cancer Institute and the Universities of Pennsylvania, Baylor, Washington, British Columbia and Toronto,” says Sondel, noting that each has a specific role in finding breakthroughs in childhood cancer treatments.
Sondel’s team – which includes Ken DeSantes, MD; Christian Capitini, MD; Mario Otto, MD, PhD; Peiman Hematti, MD; Alexander Rakhmilevich, MD, PhD; and Jacquelyn Hank, PhD ’78 – will receive $340,000 per year over four years to advance the study of immunotherapy.
In the overall care of children with cancer and related disorders, they work closely with the other faculty in his division: Carol Diamond, MD; Diane Puccetti, MD; Margo Hoover-Regan, MD; and Neha Patel, MD.
“This work is critical because research is at a crossroads,” says Sondel. “We have made strides in understanding the biology of cancer, but have not yet revolutionized therapies. The Dream Team collaboration brings together the fields of genomics and immunotherapy to accelerate development of novel cancer therapies that have fewer side effects than current treatments.”
Among other things, the Dream Team grant will help fund the next phase of Sondel’s immunotherapy research. One approach being pursued in the lab uses a genetically engineered antibody, linked to IL-2; the team will inject it directly into tumors. In addition, researchers will add a separate treatment, called “checkpoint blockade,” to try and boost the white blood cells that are already reacting against the cancer.
Sondel’s thirst for understanding tumor immunology and his deep commitment to improving survival rates for patients with childhood cancer hail to his undergraduate, premedical genetics work at UW–Madison.
“When I was a sophomore in 1969 and had a job as a janitor in the dorms, I began knocking on laboratory doors looking for a lab job,” recalls Sondel, a native of Milwaukee, Wisconsin, who loves many things about Madison, including canoeing its lakes and rivers when he can find the time. “I was really fortunate that Fritz Bach offered me an entry-level job washing test tubes.”
Fritz Bach, MD, who led the world’s first bone marrow transplants when teams at the UW and University of Minnesota performed simultaneous transplants in 1968, became Sondel’s mentor and inspired him to pursue this path. It wasn’t long before Sondel began assisting in experiments and creating his own experiments, thanks to encouragement from Bach and Miriam Segal, a graduate student.
“Fritz had a knack for mentoring people and moving projects forward,” Sondel reflects. “He knew how to focus ideas and thoughts. Fritz’s leadership energized me and others to do original work.”
In 1969, Sondel got a job as an orderly in a Milwaukee hospital, where he gained experience in a clinical setting. He decided to focus on a career as a physician and started wondering what specialty he would enjoy.
“I learned so much about different approaches to patients. Some physicians were like a whirlwind and did not spend much time with patients. Others would sit down and talk with patients until their questions were answered. This was my first exposure to the challenge and importance of listening to and communicating with patients and their families,” he says.
Upon earning his bachelor’s degree a year early in 1971, Sondel entered a UW–Madison graduate degree program and continued working in Bach’s lab. He entered medical school at Harvard in 1972.
This serious student also was becoming serious in his relationship with Sherie Katz, a young woman he met a few years earlier. After his first semester of medical school, they got engaged. Through a quick but opportune decision over Sondel’s winter break in Madison, they shared the news with their parents and got married four days later.
Back at Harvard with a new wife, Sondel quickly realized that, in addition to gaining the broad background required of medicine, he wanted to maintain his focus on the innovative immunogenetics work he had been doing. He thus took time off from medical school, returned to UW–Madison and earned a doctorate degree in genetics.
Sondel then moved back to Harvard and finished medical school in 1977. He and his wife were expecting their first child, and the happy news helped clarify Sondel’s next career decision.
“We chose to have me do my internship and residency, focusing on childhood cancer and immunology, in the Midwest near family,” says Sondel, who is grateful for his wife, four grown children, son- and daughter-in-law, and grandchildren.
In 1978, Sondel returned to Madison for a residency in pediatrics at UW Hospital and Clinics and was able to continue part-time research. He received a big break when the head of Harvard’s cancer center, Tom Frei, MD, became a visiting professor at the UW in 1979. Aware of Sondel’s work at Harvard, Frei urged Paul Carbone, MD, head of the Carbone Cancer Center that now bears his name, to offer Sondel a faculty position and his own laboratory, starting in 1980. Madison and the UW have been Sondel’s home ever since.
“I’ve had 33 incredible years as a UW faculty member; I have enjoyed the atmosphere of academic freedom, support and cooperation here at UW, along with the chance to work with really outstanding colleagues, students and postdoctoral trainees. I’ve also had the privilege of helping families of children with cancer,” Sondel reminisces. “Those inspirational families have a great deal of courage and love.”
Their courage served as the impetus for Sondel and his colleagues to create the Kids with Courage reunion. For the first such event in 1993, Sondel and his team joined forces with former patient Kelly Cotter and supermodel Cindy Crawford. Crawford has been a long-time supporter of pediatric oncology at the American Family Children’s Hospital. This relationship began because Crawford and her family spent a significant amount of time at that hospital when her brother, Jeff, underwent treatment for cancer. He died at age 4 in 1975.
Kids with Courage is held every five years and has grown over time. This year’s fifth reunion – honoring 20 years of cancer survivors – is among the most satisfying gatherings for Sondel and his colleagues who were able to highlight the last decade’s advances in immunology and other research findings that have translated into clinical benefits for patients.
Sondel notes that progress in translational cancer research requires teamwork, ideas, hard work and patience – despite the urgent need to be able to implement better treatments for children who need them now.
“Our work is about persistence – sticking with it to see improvements come steadily, but in small increments; it’s not about immediate breakthroughs,” he shares.
This article appears in the fall 2013 issue of Quarterly.