Alliance for Cancer Gene Therapy (ACGT) has awarded a collaborative research grant to two scientists at Children’s Hospital of Philadelphia who are developing a cell and gene therapy for childhood cancers.
The ACGT-Barbara Netter Fund Collaboration Challenge Award will support the work of John Maris, MD, and Stephan Grupp, MD, PhD in collaboration with the biotechnology company Hula Therapeutics on their project titled “Translating peptide-centric CAR T-cell therapies for childhood cancer.”
The collaboration focuses on neuroblastoma, which is a nerve cell cancer that occurs most often in young children and infants, although their approach could translate to other pediatric cancers and adult cancers. The ACGT-Barbara Netter Fund Collaboration Challenge Award will support a phase 1 clinical trial currently being planned at CHOP.
What is CAR T-cell therapy?
T cells are a natural and essential part of the human immune system. CAR T-cell therapy involves engineering the patient’s T cells to look for and destroy cancer cells expressing a specific protein on the cells’ surface. Scientists give the T cells a new gene that encodes a set of instructions for how to find cancer cells expressing the target protein.
How does the peptide-centric CAR T-cell therapy work?
Standard CAR T-cell therapy targets proteins on the surface of cancer cells. In neuroblastoma, most viable protein targets exist inside of the cells.
Fragments of these protein targets (peptides) still rise to the cancer cells’ surface, where they can be targeted by the immune system. T cells naturally look for these peptides to search for diseases such as viruses. This aspect of the immune system led Dr. Maris and Dr. Grupp to develop CAR T cells capable of targeting peptides on the surface of cancer cells.
Certain peptides might be expressed at higher volumes in some pediatric neuroblastoma patients than others. Dr. Maris said the goal is to build “a suite” of peptide-targeting CAR T cells for a variety of peptide targets. This effort will potentially provide more effective therapies for each individual patient.
Why are Drs. Maris and Grupp focusing on childhood cancers?
In the 1960s, just one out of 10 children with cancer defeated their disease. The cure rates have improved dramatically – four out of five children are cured of cancer now – but any child dying is still unacceptable.
This is the main reason why Drs. Maris and Grupp are tackling the challenge of pediatric cancers: to provide an effective cell and gene therapy for children with tumors that resist other treatments.
“The approach of using multiple chemotherapy drugs is not bringing children with difficult-to-treat cancers any closer to better outcomes,” Dr. Grupp said.
Approximately 50% of children with neuroblastoma have a positive anti-tumor response to chemotherapy, meaning the tumor either shrinks or disappears completely. The other 50% do not have another treatment option proven to work against neuroblastoma.
Making the challenge greater is the lack of funding for childhood cancer research. There are fewer pediatric cancer patients than adult cancer patients, and funding sources prioritize the larger patient population.
The sparse funding means fewer scientists focused on childhood cancers – which leads to less research in general. Drs. Grupp and Maris aim to reverse this trend – conducting crucial research that could develop new therapies and train new pediatric scientists – and funding from ACGT is a crucial ally.
“I can’t emphasize enough how important this funding is,” Dr. Grupp said.
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