Phase 1 Study of Autologous Activated T Cells Transduced with a Third-Generation GD2 Chimeric Antigen Receptor, Coexpression of IL-15, and iCaspase9 Safety Switch
Abstract
While there has been dramatic improvement in outcomes in pediatric hematologic malignancies over the past 30 years, children with high-risk solid tumors continue to have a poor prognosis. Specifically, children with high-risk neuroblastoma require therapy with chemotherapy, surgery, radiation, stem cell transplantation, and differentiating agents to achieve a disappointing 50% overall survival rate. A novel approach has recently obtained exciting antitumor responses in patients with leukemia. This therapy is based on the infusion of a subset of blood cells isolated from the patients themselves called T lymphocytes, and modified in a specialized laboratory to express a molecule that renders them better at killing tumors. These highly antitumor specific T cells are called Chimeric Antigen Receptor T cells, or CAR-T cells. However, responses have not been seen in solid tumors, like neuroblastoma. Thus, patients with high-risk, refractory, and relapsed neuroblastoma are in critical need of novel therapy. We have developed in our laboratory a novel way to improve the antitumor activity of these CAR-T cells by enhancing their potential for survival and efficacy at the tumor site. These goals are achieved in a safe way, as these T cells will also carry a specific safety switch that will minimize any potential side effects. We propose to assess the safety and improved efficacy of our approach in a Phase I clinical trial for children with relapsed/refractory neuroblastoma and identify laboratory tests that will predict responses and outcomes. These novel and improved CART cells have the potential to influence the direction of therapy directly for neuroblastoma and also for other solid malignancies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010890
Entities
People
- Barbara Savoldo
Organizations
- United States Army
- University of North Carolina at Chapel Hill