Vaccine-Boosted Tumor Microenvironment-Restricted Multi-Antigen Targeting CAR T for Pediatric High-Grade Gliomas
Brain tumors pose a significant challenge in pediatric oncology and are among the leading causes of cancer-related deaths in children in the United States. Among these, Pediatric High-Grade Gliomas (pHGG) make up about 10% of all brain and central nervous system tumors. These tumors are particularly aggressive and have a very poor prognosis. Patients with pHGG tumors like diffuse intrinsic pontine gliomas (DIPG) typically do not survive more than two years, and there are not many treatment options available for them. Therefore, there is a desperate need for the development of new therapies that can improve the outcomes of these patients. One potential approach is Chimeric Antigen Receptor (CAR) T cell therapy, in which the patient's immune cells are modified to specifically recognize and kill tumor cells. This method of immunotherapy has shown promise in treating blood cancers but has not yet been as successful with solid tumors. In this project, we aim to address this challenge by developing a CAR T therapy that targets multiple antigens. To ensure the safety of the therapy, we will restrict the activity of CAR T cells only to the tumor site. The goal of this project is to improve the treatment's effectiveness while minimizing any unwanted effects on healthy tissues.
Project Goals
The main goal of this project is to develop an effective and safe therapy for patients with a highly aggressive type of brain tumor called pediatric high-grade gliomas. To achieve that we will develop a novel and effective method of immunotherapy in which a patient’s immune cells will be engineered to recognize and attack brain tumor cells. Additionally, we plan to create a system that enables us to engineer therapeutic cells to recognize and respond to the specific features of the tumor site in pediatric brain tumors. This therapy will be safe because we will ensure that the engineered immune cells only activate in the tumor site, which is a major concern when developing immunotherapies. To guarantee this safety, we will investigate the mechanisms of the therapy using different preclinical brain tumor models. We will study how the therapy works and find ways to improve it so that it can be used successfully with pediatric brain cancer patients. Our ultimate goal is to provide a targeted and potentially curative option for a disease with limited effective treatments available. This project is a crucial step in the development of therapies that can treat all types of pediatric brain tumors in the future. We hope that our research will pave the way for more effective treatments that can save the lives of pediatric brain cancer patients.
