In 2014, Dr. Pat Reynolds (pictured above) received a grant from ALSF to maintain and expand The Childhood Cancer Cell Repository.
By: Trish Adkins
Every year childhood cancer steals 11.5 million future years of healthy life away from children, according to a World Health Organization study conducted in 2017.
Childhood cancer doesn’t just rob children of their lives; it also robs them of their quality of life. Toxic but effective therapies make being a typical kid during treatment impossible, resulting in missed school days, activities and more time in the hospital. Down the line, these treatments can cause more devastating side effects like cardiac myopathy, resulting in premature heart failure and other chronic health issues.
And, the children with cancers that cannot be effectively treated—as high as 70% of children in low-to-middle income countries fall into this category—lose their lives altogether.
Still, childhood cancer is relatively rare around the world, as compared to adult cancers. While this does not make research less critical, it does present research challenges. Recruiting and filling clinical trials is hard when there is a small population of kids who could be eligible. And, as oncology treatment and research continues its laser focus on precision medicine, finding viable samples to use in pre-trial studies can be difficult and creates a financial strain on pediatric oncology research labs that are already underfunded—especially as compared to adult oncology labs.
But, in Lubbock, Texas at the Texas Tech University Health Sciences Center, one researcher funded by Alex’s Lemonade Stand Foundation (ALSF) is leading the charge to ensure researchers around the world have access to a secret weapon that can accelerate their research: tumor models and cell lines.
“You can’t get this anywhere else.”
Dr. Patrick Reynolds has spent decades studying cell lines and cancer tissue. In 2014, Dr. Reynolds received a grant from ALSF to maintain and expand The Childhood Cancer Cell Repository. Since that time, and with additional support from the Children’s Oncology Group (COG), the Cancer Prevention & Research Institute of Texas, National Cancer Institute and the Department of Defense, the Repository has generated and banked 620 continuous patient-derived cell lines (tumor cells growing in test tubes) and 120 patient-derived xenografts (PDXs) which are tumors grown directly in specialized mice.
Dr. Reynolds sees the repository as a highly collaborative, living resource. Beyond the cell lines and PDXs, the Repository offers genomic data, a space to share information and constant collaboration.
Everything is available to any researcher who asks, free of charge.
“Because of ALSF support and how we’ve chosen to run the Repository, we don’t have to worry about charging people for anything,” said Dr. Reynolds. “You can’t get this anywhere else.”
Researchers from over 500 labs in 30 countries have come to the Repository for support for their research and received it. When they ask Dr. Reynolds for sequencing data, if he has it, he will pull it and share it. The data sharing works both ways, with teams who use models and cell lines in their work sharing data and study results with the Repository.
For researchers around the world, this collaboration can accelerate the pace of their discovery and help them avoid duplicating testing that has already been done.
“Everyone at the Repository is absolutely committed to making childhood cancer research better”
“The important thing about the Repository, there are other repositories but they are more cumbersome to access and more expensive and less collaborative,” said Dr. Reynolds. “When a researcher contacts us, our response is always ‘How can we help you get it? Tell me what you need?’”
In addition to the financial support of ALSF and other funders, what makes all collaboration and research happen is the tumor and tissue donations from families facing childhood cancer.
Powered by Donations
All the tumor and blood samples the Repository receives are donated from children with cancer. Parents can consent for a sample from surgery or a biopsy or blood draw to be donated at diagnosis, relapse or at any point during treatment.
When these donations are received, they are immediately processed and if there is a large enough sample, the Repository does two things.
First, some of the sample is placed in cell culture and used to grow cell lines. Those cell lines can used in a lab for a variety of studies. At the same time, the team takes tissue directly from the donated sample and places in an immunocompromised mouse to generate a tumor model (PDX).
Doing these things from the original sample minimizes selective pressures. Selective pressures can cause the tumor to change or mutate because of the environment it is placed in. The Repository team also does other things like setting up the cell lines in all oxygen conditions--leaning on the knowledge that different cells thrive in different oxygenation levels.
They also track and document when in the diagnosis and treatment a sample was taken as well as the status of the patient as they continue treatment—to ensure researchers have a thorough understanding of how treatment has impacted the tissue sample and how a child responds to treatment even after donation.
Tumors can also be donated after a child dies and then named by their families. This is a meaningful gift and one that researchers hold in high regard. These named cell lines give researchers important scientific insights to the deadliest tumors and they give them the very real motivation—a child’s life—to power their research.
To Cures for All Children with Cancer
Dr. Reynolds points to several incredible stories from donations to the Repository. One cell line, named Felix, after the donor who died from ALK-driven neuroblastoma at age 6, has been used to power research into the same type of neuroblastoma that took his life, leading to late phase clinical trials and impacting children on that trial—giving them not only healthy days but the very future that neuroblastoma threatened. Another cell line, Fly623, named for Alex Podeswa who also battled ALK-driven neuroblastoma and died at age 14, has been used in research studies and clinical trials.
Could These Cell Lines Cures Neuroblastoma? The Alex Podeswa Story
Last year, Dr. Reynolds and his team made a game changing discovery using model and cell lines from the repository and found a therapeutic agent that has the potential to reverse chemotherapy resistance.
Also, the discovery and collaboration made possible by the Repository is accelerating the testing of precision treatments for all types of childhood cancer and getting those agents into clinical trial. Those advancements directly impact children with cancer now and will help those who are diagnosed in the future.
“None of this would happen without having these robust models,” said Dr. Reynolds.
The Childhood Cancer Repository is funded in part by ALSF and generates patient-derived cell lines (PDCLs) and patient derived xenografts (PDXs) from tumor, blood, and bone marrow samples provided by the Children’s Oncology Group. The repository has generated and banked 620 continuous PDCLs and 120 PDXs from childhood cancers. The Repository serves more than 500 labs in 30 countries, giving researchers around the world free access to the tools that could lead to more cures for children.
Learn more about the Repository here