The DeRenzo lab studies CAR T cell therapy to optimize treatments for children with solid tumors.
Solid tumors are notoriously difficult to treat. The body’s natural immune system is often ineffective against the aggressive nature, immunosuppressive qualities, and complex cell composure of solid tumors. The goal of our laboratory is to explore treatments that bolster the body’s natural immune system—an approach called immunotherapy—to optimize the treatment of solid tumors in children. To achieve this, we develop and improve methods for training patients’ T cells to target and kill cancer. Through this work, we aim to discover how to leverage immunotherapy for the treatment of pediatric patients with solid tumors.
In our work with immunotherapy, our laboratory focuses on developing new chimeric antigen receptor (CAR) T cell therapies, discovering methods to improve CAR T cell function, and learning how we can apply them effectively to treat pediatric patients with solid tumors.
To maximize the potential benefit of T cell therapies, we develop CAR T cells to target antigens found on multiple pediatric solid tumor types. Our work in this area focuses on neuroblastoma and sarcomas, specifically osteosarcoma, rhabdomyosarcoma, and Ewing Sarcoma. In collaboration with the Solid Tumor Team and the Departments of Computational Biology, Immunology, and Pathology, we examine potential new targets for pediatric solid tumors, develop novel CAR T cells to target these antigens, and determine how to implement cutting edge CAR T cell therapies to treat patients in clinical trials.
We are currently conducting the first clinical trial using CAR T cells to treat patients with solid tumors at St. Jude. Our goal in this trial is to determine the safety and antitumor activity of a new CAR T cell therapy that can be used to target a variety of pediatric solid tumors.
We will take information gained from this study to explore why the treatment works in some patients and not in others. In collaboration with the Departments of Immunology, Pathology, and Interventional Radiology, we will analyze blood and tumor samples to understand changes within CAR T cells and tumor cells after treatment and determine how we can further modify CAR T cell therapies to improve outcomes for patients in future clinical studies.
Through all aspects of our work, the shared resources and collaborative spirit of St. Jude enable us to maximize the impact of each study we do. This leads to the performance of world-class science in the CAR T cell arena. We are able to perform reverse-translational research, in which our examination of patient samples helps guide development of future therapies.
We collaborate with the Departments of Immunology and Computational Biology to analyze single T cell profiles and look at T cell receptor specificity over time. A further collaboration with the Department of Immunology allows us to perform epigenetic sequencing of T cells to examine methylation profiling to discern if there are any epigenetic changes that occur in this process. The ability to examine these aspects of CAR T cell therapy by reverse translational approaches is a unique opportunity in our effort to improve treatments for pediatric patients with solid tumors.
While our current work focuses on the application and optimization of CAR T cell therapy, we would like to understand the basic biology of CAR T cell mechanistic function as a potential future area of study in our laboratory.