Study of Genetically Engineered T Cells with Interleukin-15 and -21 for Children and Young Adults with GPC3-Positive Solid Tumors

What this Trial Is About

This trial studies children and young adults with GPC3-positive solid tumors, including pediatric liver cancers and other rare tumors. It evaluates an experimental treatment using specially engineered immune cells called CARE T cells. These T cells are designed with a gene that helps them recognize and kill tumor cells more effectively by combining antibody and T cell technologies. The study aims to find the highest safe dose, understand how long the cells last in the body, monitor side effects, and assess treatment impact. Participants will have their T cells collected and genetically modified with a retrovirus to express GPC3-CAR and proteins IL15 and IL21, which help the cells grow and persist. Before receiving CARE T cells, participants undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine for 3 days to reduce existing T cells. The frozen CARE T cells are then thawed and infused over 5 to 10 minutes, 2 to 4 days after chemotherapy. The study uses a dose-escalation design with increasing doses tested in groups of at least three participants. Participants are monitored extensively before, during, and after treatment with physical exams, blood tests, tumor scans, and optional tumor biopsies. Blood samples are collected at multiple time points up to 15 years to study the persistence and activity of CARE T cells and detect long-term side effects of the gene therapy. Participants will also be asked yearly about their health for ongoing safety monitoring. The total participation for this study can last up to 15 years to ensure thorough follow-up.

Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors