Ensuring the Continuity of Research to Improve Children’s Lives Amidst the Unexpected

Seattle Children’s Therapeutics is envisioning and testing next-generation cell and gene therapies for pediatric diseases so children have the medicines they deserve.

How Seattle Children’s Therapeutics is Navigating the Pandemic

When the World Health Organization declared COVID-19 a global pandemic in March 2020, Seattle Children’s Therapeutics researcher Kaori Oda worried that her research work would be put on hold, or even worse, need to permanently end. Like most people, she was worried that she and her family might contract the virus, but she was also concerned that a slowdown would impact her team’s timeline for bringing a much-needed therapy to children with leukemia.

Seattle Children’s Therapeutics is a unit in the research division at Seattle Children’s. As a novel non-profit therapeutics development enterprise, it is devoted to envisioning and testing next-generation cell and gene therapies for pediatric diseases, so children have the medicines they deserve.

The Seattle Children’s Therapeutics team has designed, manufactured and launched a robust portfolio of cellular immunotherapy clinical trials for childhood cancer since 2012 in the areas of leukemia, lymphoma, brain tumors and solid tumors. The team plans to expand its focus to other childhood diseases that are amenable to treatment using genetic and cellular therapies.

At a time when several large U.S. research institutions closed the majority of their laboratories and offices, the Seattle Children’s Therapeutics team had to make some difficult choices. Dr. Josh Gustafson, director of research and development, was at the center of the decision tree. He and other leaders had to determine which research projects would be most severely impacted if they did not move forward at the same pace as they did before the pandemic; what to do about ongoing experiments involving cultures and other active or sensitive materials; which teams absolutely had to come in to conduct the research in person; what would happen if those team members weren’t comfortable coming in; and whether months and years of hard work would have to be put on hold or scrapped altogether.

As a research scientist at Seattle Children’s, Oda’s role cannot be performed at home. Three times a week, she carefully administers small doses of an investigational therapy to animal models and then records information about each animal’s behavior.

Kaori Oda is research scientist III at Seattle Children’s Therapeutics.

“Throughout the pandemic, my team has never stopped,” said Oda. “Because of the nature of our research, a team member is needed onsite at all times. So we set up a schedule so that someone was there all the time, but we were never there together.”

Patient and precise by nature, Oda studied to become an architect in Japan. When she moved to the U.S. to study at Western Washington University, her professors noticed her aptitude for science and recommended she pursue a career in research. That led her to her current position at Seattle Children’s.

“We are getting fantastic results because of our teamwork,” said Oda. “We have helped and encouraged each other throughout the pandemic, and we figured out how to make it all work.”

Gustafson agrees.

“The challenge with the type of research we do in R+D is that it has to be done in person. You can’t bring biological materials home and do this work at your kitchen table,” said Gustafson. “But the team stepped up. They were enthusiastic about coming in and continuing to work because they are deeply committed to the work we do to find better treatments and cures for children. And that really speaks to the culture here of putting our work for children first and foremost.”

May 2020 brought a new set of challenges exacerbated by the pandemic. First, there was the Seattle Children’s Therapeutics R+D and Correlative Studies teams’ scheduled move to Seattle Children’s newest research building, known as Building Cure. More than 30 scientists, their laboratories, offices and 30 years of research data and equipment had to be moved in a socially distanced manner with atypical limited in-person operational resources due to the pandemic.

Dr. Josh Gustafson is director of research and development within Seattle Children’s Therapeutics.

“Our scientists and other team members therefore needed to be very involved in the move and they were critical to ensuring minimal interruption to operations,” said Gustafson. “They had to be very purposeful about arranging space and workflows to make sure people did not work too closely together. We had some bumps along the way in June and July while settling in, but by August we were hitting the ground running. It was really inspiring to see everyone working together to make it happen.”

Also in May, thousands of people marched in the Seattle area to express their outrage over the murder of George Floyd in Minneapolis. The marches sometimes involved tens of thousands of demonstrators, which were in close proximity to Seattle Children’s research facilities, making it challenging for the Seattle Children’s Therapeutics team to come and go.

“These were complications we could not have predicted,” said Gustafson. “I never thought that I would have to tell the team that we have heard that there’s a march heading towards the Seattle Police Department’s West Precinct, which is kitty corner from our building, and that everybody should depart the building within a half hour.”

Oda lives just a few blocks from the Seattle Police Department’s East Precinct station, which was the site of many demonstrations.

“That was a scary period for me to come to work,” she said. “While I wasn’t concerned by the demonstrators, I was concerned about potential random attacks and racism.”

But she diligently kept coming in.

The full impact of COVID-19 hit Marilyn Sanchez in October, when basic research supplies she orders to keep the labs going were diverted to research facilities around the country devoted to making COVID-19 vaccines. As manager of therapeutics laboratory operations, Sanchez ensures that the scientific team has the supplies they need readily at hand. She is responsible for ordering everything from glass pipettes and chemical re-agents to flow cytometers and centrifuges.

Marilyn Sanchez is manager of Seattle Children’s Therapeutics laboratory operations.

“Normally, we have a good stockpile of items that our scientists need and we know how long it takes to obtain orders from our vendors. COVID-19 changed all that. All of a sudden, items that normally take weeks to obtain were taking six months and longer,” she said. “Our scientific teams would come to us and say they needed something urgently, and my team and I had to find a way to get it in collaboration with our partners in the research purchasing team.”

Originally from Puerto Rico, Sanchez earned her master’s degree in pharmacology and toxicology at Washington State University.

“As the eldest of six children, I began managing people from an early age. It’s a natural skill that I take into operations – organizing people and making sure everything in the environment is running smoothly,” she said. “I tried to work from home in the beginning of the pandemic, but I found it wasn’t very efficient, given the nature of my job. And since I was asking my team to come in to work, I wanted to be there too.”

Gustafson credits his team and Trinh Pham-Dembinski, vice president of operations and finance for Seattle Children’s Therapeutics, with handling the difficult decisions of 2020 exceptionally well.

“The entire Seattle Children’s Therapeutics team and our partners in Center Support Services have remained steadfastly dedicated to their work to support Seattle Children’s mission,” he said. “I am so proud of this team for stepping up in spite of fear, uncertainty, and fatigue to perform at a high level day in and day out. Trinh has been an incredible advocate and motivational leader, enabling us to maintain operations and a strong business stance through everything that’s happened in the past year.”

Gustafson, Oda and Sanchez are looking forward to getting back to normal, however.

“We have built an intentional therapeutics development machine that is very exciting to be a part of,” said Gustafson. “We have received several inquiries from companies and organizations interested in collaborating with us, which is incredibly exciting. But the best part is that we get the opportunity to integrate innovative technologies into our clinical pipeline to improve the lives of children around the world. Our technology and research breakthroughs in drug development are going to revolutionize treatment of many different childhood diseases.”

The Therapeutics Cell Manufacturing facility translates laboratory discoveries into investigational treatments.

Despite all the challenges of 2020, Seattle Children’s Therapeutics’ dedicated efforts produced significant results. Of note, the team working on a therapeutic product to combat Acute Myeloid Leukemia (AML) completed preclinical studies, and Oda’s animal models were a key component in achieving this milestone. Enrollment for a clinical study is expected to open in the first quarter of 2022.

Another Seattle Children’s Therapeutics team completed preclinical development for the next generation of therapies to treat brain tumors with cell therapy by attacking multiple tumor targets (Brainbow).

Seattle Children’s Therapeutics also launched a strategic initiative, VectorWorks, to make their own viral vectors. Viral vectors carry specific genetic information, such as instructions to make Chimeric Antigen Receptors (CARs), into target cells and then are inserted into the genome. By manufacturing their own vectors, Seattle Children’s Therapeutics can dramatically cut the costs and wait time associated with contract manufacturing with outside vendors, as well as provide vectors to others, filling a huge need given the shortage of organizations making vectors.

VectorWorks’ products will provide patients at Seattle Children’s and beyond with access to medicine that they would otherwise have to wait years to receive.

“The resilience and dedication of the entire Therapeutics team, from R+D to the Therapeutic Cell Production Core, Clinical Development, Correlative Studies, and Business Operations, is to be celebrated,” said Gustafson. “The silver lining of 2020 is that we got to really understand the strength and the depth of our entire team’s commitment to the kids we serve. It’s always going to be kids first.”