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From Philly to Rio: CHOP’s Mission to Lower CAR-T Therapy Cost
By Kate Knab
When Associate Director of the Cell Based Therapy Laboratory (CBTL) at Children’s Hospital of Philadelphia, Stephan Kadauke, MD, PhD, attended Carnival in Rio de Janeiro, Brazil, he’d only planned on visiting a friend. But when an opportunity arose during that visit to form a global partnership that could help establish a chimeric antigen receptor T cell (CAR-T) program in Brazil, Dr. Kadauke pursued it.
CAR-T cell therapy is a form of cancer immunotherapy that involves the genetic modification of a patient’s own immune cells to recognize and kill cancer cells. Traditional CAR-T cell manufacturing is expensive, in part because it’s a multi-step complex process that requires highly trained staff to operate multiple machines.
With years of treatment experience beginning with Emily Whitehead in 2012, and a new $4 million grant from the Brazilian Ministry of Health, of which CHOP received $1.2 million, CHOP physicians and scientists led by Dr. Kadauke now aim to introduce this life-saving therapy to low and middle income countries at a fraction of the cost of commercial cell therapy products.
They kicked off this mission with a site visit to their partners and key stakeholders at the National Cancer Institute (INCA) of Brazil in Rio Sept. 9. Delegates representing high levels of leadership in both CHOP and INCA met to align on building a CAR-T clinical program that is safe and efficient, performing the first full-scale CAR-T manufacturing run with input and advice from the CHOP team.
“Working together with Brazil is the beginning of a much larger global initiative to try to bring cell and gene therapy at an affordable price point to places where it’s needed,” Dr. Kadauke said. “Here at CHOP, we have one of the most promising approaches.”
A low-middle income country of 200 million people, Brazil already performs blood and bone marrow transplants, and the Brazilian Health Regulatory Agency (ANVISA) approved the first commercial CAR-T product in 2022. While CAR-T therapy is now generally available for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia in Brazil, the public health system struggles to pay its steep price.
As part of the larger effort to make these therapies more affordable, Rio’s CARioca Initiative – derived from an indigenous term, “carioca” refers to a person from Rio – aims to leverage a network of now-defunct cord blood banks distributed throughout the country as space for automated CAR-T cell manufacturing using a closed system platform called the Prodigy®.
Although similar to traditional clean rooms in which Good Manufacturing Practice (GMP) standards must be maintained to produce clinical-grade products, the cord blood banks operate at less stringent air handling conditions. However, with its closed system set-up, the Prodigy machine maintains its own GMP environment, reducing the need for stringent air handling to produce clinical-grade CAR-T cells. The automation capabilities also reduce the training needed for specialized technologists, all key factors that broaden access and reduce cost.
“If you want to do the kind of true outreach that helps a large number of people instead of a lucky few, you need to do it at the point of care where people need the therapies,” said Stephan Grupp, MD, PhD, director of CHOP’s Kelly Center for Cancer Immunotherapy, its Cancer Immunotherapy Program and Chief of the Cellular Therapy and Transplant Section (CTTS).
Leading this initiative on the Brazilian side is Martin Bonamino, PhD, head of INCA’s CAR-T Cell Therapy Program. Dr. Grupp’s expertise helped to establish the infrastructure needed to manufacture the lentiviral vectors the Brazilian facilities will use to get started.
The site visit was the first of multiple reciprocal visits planned over the next two years between CHOP and INCA scientists as they refine protocols and processes. Although the product generated by Dr. Kadauke and his collaborators on the machine's inaugural run will not be delivered to patients, the test run will demonstrate the machine’s and the team’s ability to produce a clinical-grade CAR-T product. The product also will undergo the same testing a clinical product would for safety, purity, and potency, which is a critical step toward obtaining approval from ANVISA to begin clinical trials and treating patients.
“We want our work to amount to a successful technology transfer that will enable Brazil to make these products independently within two years or so,” Dr. Kadauke said, “but we hope our collaboration will continue beyond that.”
In addition to supervising the manufacturing run, the CHOP delegation met with more than 30 key stakeholders at INCA to take a deep dive into all aspects of running a pediatric CAR-T clinical program. In meeting with clinical departments such as hematology and pediatric intensive care, and ancillary services such as apheresis and pharmacy, the CHOP and INCA team jointly discovered gaps and discussed approaches that will ultimately allow INCA to treat their first patients safely and successfully.
Looking ahead, Drs. Kadauke and Grupp are optimistic about Rio as the launch point for bringing affordable cell and gene therapies to low- and middle-income countries. While cancer remains a central focus, they are also exploring how this collaboration could pave the way for cost-effective gene therapy options for other diseases, such as sickle cell disease, which affects thousands globally, including in the Philadelphia area and regions like Bahia, Brazil.
The ultimate goal is to establish a flexible, scalable system that delivers life-saving treatments for a fraction of the current cost, accessible to patients around the world.
“The CBTL and CTTS at CHOP make things happen,” Dr. Grupp said. “Execution is everything. We do things practically, we focus on delivery, and we’re proud that we can help give these therapies to patients knowing that they work.”