Pediatric oncologist uses patient-centered approach to drive CAR-T innovation
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Shannon L. Maude, MD, PhD, always knew she wanted to work with children — she just didn’t always know how she could best help them.
Presently an assistant professor of pediatrics at Children’s Hospital of Philadelphia (CHOP) and medical director for Center for Cellular Immunotherapies at University of Pennsylvania School of Medicine, Maude originally thought she might be a teacher. The results thus far suggest she made the right choice to go into medicine after majoring in biology at University of Virginia.
“I think what I always liked about oncology is that there is such a strong tie between the research and clinical practice,” she told Healio. “I think more than in any other field, there is a really powerful link between what we learn from patients and how that impacts the research and new treatments that come down the pike.”
Maude’s original scientific interests were more biologic in nature, in the field of signal transduction. But her exposure to the innovative work being done in laboratories at CHOP and University of Pennsylvania as a research fellow led her down a path that would make her a leader in the field, developing insights into clinical care of cellular therapy recipients that is driving innovation in how they are delivered.
“What I’ve enjoyed the most about the experience is that there’s so much science that goes on in the day-to-day care of these patients,” she said. “We really are learning from every single patient who we treat and can take that back to the lab to learn from and then help optimize these therapies.”
And that’s the driving force behind Maude’s work. She didn’t invent chimeric antigen receptor T cells, but she got to be on the ground floor of their delivery. Ever since, Maude has been in pursuit of ways to make them more effective, safer and produce a better overall quality of life for her patients.
A Philadelphia story
With her undergraduate education completed, Maude — a Philadelphia region native — returned home and enrolled in the MD/PhD program at University of Pennsylvania School of Medicine.
At Penn, Maude fed her initial interest in lab work that she developed while doing an independent study project at University of Virginia. Add to this a desire to go into medicine — specifically, cancer research — after a physics class sparked her curiosity to learn about radiation oncology.
Maude then completed her fellowship in pediatric hematology and oncology at CHOP in 2012, and she’s remained in Philadelphia ever since.
“I’m a lifer,” Maude — a devout Eagles fan— said proudly.
And why would she look elsewhere, as she explained. Not only are Penn and CHOP world-class institutions in her opinion, but being there at that particular time meant participating in one of the most impactful scientific developments for cancer treatment in recent memory.
There from the beginning
Maude’s original clinical care and research interests in the cancer field involved pediatric acute lymphoblastic leukemia. She started doing research in signal transduction but wanted to work on something “directly relevant to patients.”
At the time Maude was finishing her fellowship, the first CAR-T trial opened at CHOP under the direction of Stephan A. Grupp, MD, PhD, section chief of cellular therapy and transplant, inaugural director of the Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy and founder and director of the cancer immunotherapy program.
In Grupp’s lab she was part of the team that treated Emily Whitehead, a young girl who became the international face of CAR-T as the first patient with ALL to achieve remission after receiving the experimental therapy.
Whitehead recently celebrated a 10-year remission milestone. During that intervening decade, Maude was part of a group led by Grupp and other colleagues, including Carl June, MD, of the University of Pennsylvania, who conducted the registrational trial of tisagenlecleucel (Kymriah, Novartis), which subsequently became the first commercially available CAR-T product when the FDA approved it for younger patients with B-cell ALL in 2017.
The fact that Maude has been a part of so much so early in her career is a testament to her extraordinary capabilities as a researcher and clinician, according to Grupp.
“She is an exceptional person, and her patients just adore her,” Grupp told Healio.
“Shannon is a multifaceted individual who brings to the table an incredible, discerning intellect and an unbelievable command of the details,” he said. “It is reflected in the fact that she joined our efforts so early in her career and was an extremely important part of the initial development of the product that ended up being Kymriah.”
As Grupp explained, Maude has parlayed this experience into a career spearheading “incredibly important work” to improve the effectiveness of cell therapies.
Among these are studies exploring the feasibility of CAR-T retreatment when younger patients with B-cell ALL experience disease relapse after initial therapy with CD19-directed CAR-T. This includes an ongoing study looking at the use of a “humanized” CAR-T strategy that could limit immune-mediated rejection of T cells and lead to improved persistence of CAR T-cell therapies.
Grupp also pointed to Maude’s work leading an international clinical trial through the Children’s Oncology Group examining front-line use of CAR-T in younger patients with B-cell ALL. The goal of the approach is to increase durable remission rates for those at very high risk of disease relapse.
“Moving the field of CAR-T into earlier use is one of the questions that always comes up,” Grupp said. “I believe this is an area where Shannon’s research is having an ongoing and potentially significant impact.”
Grupp made certain to drive home the most “extraordinary characteristic” that Maude possesses: her amazing work ethic.
“Everybody says that they work hard, because many of us do,” he said. “But Shannon is one of the most hardworking people I’ve ever worked with in my entire career at Harvard and at Penn.
Answering the call
Despite recent efforts to promote gender equity and diversity, Maude says women are still underrepresented at the upper echelons of oncology and pediatrics. It is something she said is typical in the field of medicine across disciplines but is perhaps a bit more unfortunate in pediatrics since a higher proportion of its practitioners are women.
Nevertheless, Maude acknowledged that diversity on all fronts has moved in the right direction for science and medicine since she started her career.
“I do think that there has been a focus on gender diversity, and beyond to overall diversity and inclusion,” she said. “Things are starting to improve, but I think it will take some time and even further investment to see the full effects of these efforts.”
Maude feels fortunate to have come up under the guidance of some impactful female mentors in the field and is encouraged by the number of women who are taking their place in leadership positions.
She feels a duty to play her part as an emerging mentor in cancer care and promote diversity on all fronts, but she has special interest in providing younger women with opportunities to explore their interests and demonstrate their talent.
“I believe it is important to have diversity of mindset in all forms because it advances the quality of the science,” she said.
Despite being involved in the development of the first commercial CAR T-cell therapy and forging a name for herself as a leader in CAR-T clinical care, Maude is still relatively early in her career as a physician-scientist. It’s this relative proximity that she brings to the table for the next generation of scientists who come through her clinical research program at CHOP.
“Often, I’m closer to where they are in their career path, so I take a collegial approach that we’re working together on projects,” Maude said. “But I definitely try to allow my younger colleagues to take the research where they want it to go and bring their own ideas to the research — let them run with that and fly — while providing them support based on what I have learned.”
Mentorship is a major area of focus for Maude, not just for those she works with at CHOP but for younger colleagues in the field of pediatrics and cellular therapy, according to Grupp.
“Pediatrics is a field that has a lot of women entering it — which is very exciting,” he said. “Shannon feels an incredible drive to help these young women deal with the academic world.”
Her guidance isn’t limited to only young women in the field, he added.
“She spends a lot of time paying attention to her role as mentor and it has become a real issue for her in the most positive way possible,” Grupp said. “I think she really feels a calling to help these younger professionals.”
Making a good thing even better
Maude started her career as a disease specialist focused on treatment of ALL in children but feels she has evolved into a “cell therapist” as well.
“Our role as cell therapists is to optimize the care of our patients using the experience we have gained from deploying these therapies,” she said. “Now we need to think outside of the box so we can adapt them to other diseases.”
She expressed pride about being part of the team that developed the first commercially available CAR-T and even more so that the first indication came in pediatrics because “it is almost unheard of and a very rare thing.”
For now, however, Maude is focusing her talents on optimizing cell therapies for ALL. One important question that vexes her is why CAR-T produces durable remissions in some patients and not in others.
“I will continue to study and find new options for patients for whom this transformational therapy has unfortunately failed or not been durable enough,” she said. “That’s really where I hope to continue to have an impact — in developing these therapies and coming up with more effective options for those patients who need it most.”
The goal of Maude’s work is to provide treatment options for children with leukemia who would otherwise have none because all currently available treatment options have failed.
“I work every day to learn from our patients and advance their available treatment options,” she told Healio.
“Even in the situations when — unfortunately — our therapies do fail, I think we have seen [CAR-T] provide multiple benefits,” she added. “The ultimate goal is to cure all these children, but in the process, I hope we can also improve the quality of the time they have left to live.”
For more information:
Stephan A. Grupp, MD, PhD, can be reached at grupp@chop.edu.
Shannon L. Maude, MD, PhD, can be reached at maude@chop.edu.
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