Main Objective of the Program: Our goal is to develop new and innovative treatments for children with certain hard-to-treat cancers that express high levels of a marker called GD2. This approach involves both targeting the cancer cells themselves as well as certain elements of the tumor microenvironment, a system of cells surrounding the tumor that helps it grow and resist therapy. We will use cutting-edge advances in two rapidly evolving scientific fields, immunology and synthetic biology, to execute the studies in our proposed program and advance the development of these direly needed therapies. Why This Research is Crucial: GD2 is a marker that is expressed at high levels in some of the ...

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Main Objective of the Program: Our goal is to develop new and innovative treatments for children with certain hard-to-treat cancers that express high levels of a marker called GD2. This approach involves both targeting the cancer cells themselves as well as certain elements of the tumor microenvironment, a system of cells surrounding the tumor that helps it grow and resist therapy. We will use cutting-edge advances in two rapidly evolving scientific fields, immunology and synthetic biology, to execute the studies in our proposed program and advance the development of these direly needed therapies. Why This Research is Crucial: GD2 is a marker that is expressed at high levels in some of the most difficult to treat childhood cancers including neuroblastoma, osteosarcoma, and certain brain tumors such as diffuse midline glioma. Several treatments designed to target GD2 have been proven safe and shown promising clinical responses. However, the success rates of these treatments are still quite low, especially when compared to responses seen in patients with blood cancers. This is due to several reasons including that the therapy may not reach the site of the tumor, the tumor microenvironment prevents the therapy from working effectively, or the cancer changes to evade treatment. The Projects: Project 1 - Focusing on Neuroblastoma: Led by Dr. Heczey, this project will explore a new kind of therapy that uses a special type of cell called a natural killer T (NKT) cell, engineered in the lab to attack cancers expressing GD2. While an ongoing clinical trial for NKT cells targeting GD2 has shown promise in treating patients with neuroblastoma, the investigators found that a FDA-approved drug called etanercept might improve the effectiveness of their treatment and reduce harmful side effects. As part of their proposed program, they will test this idea in a clinical trial, where patients will be treated with either the NKT cell therapy alone or combined with etanercept. Project 2 - Attacking Pediatric Brain Tumors: Dr. Omer's team will use insights from an ongoing trial to experiment with different methods of delivering tumor-specific T cells into the body, including injecting them directly into the brain. Dr. Omer and his team will also examine the body's response to treatment, using advanced technologies to find signs that might predict how well the treatment works or what side effects it might have. Another exciting part of their work aims to make brain tumor cells more vulnerable to their treatment using specific drugs. Project 3 - Improving Treatment of Neuroblastoma and Osteosarcoma with Engineered NK Cells: This project, led by Drs. Parihar and Navai, will focus on improving the safety and efficacy of a T cell therapy that they are currently testing. They are using a type of cell called a natural killer (NK) cell, which has been modified to help GD2-specific T cells work better and reduce side effects. These engineered cells could weaken the cancer's defenses and make the tumor microenvironment less hostile for the therapeutic cells. Supporting the Projects: Administrative Core (Core AC): Under Dr. Metelitsa's guidance, this group is the backbone of the program, ensuring that all the different parts work together smoothly. This core will organize meetings, keep track of progress for the three projects, and handle reporting to CPRIT. Clinical Research Core (Core 1): Led by Dr. Wang, this team is essential for making sure the clinical trials are conducted properly. This core will take care of complex regulatory requirements and ensure that every step of the research is done according to the standards required by various regulatory agencies. Manufacturing Core (Core 2): Dr. Lapteva and her team are responsible for producing the therapies that the researchers will test in patients. They follow strict guidelines to ensure that these treatments are safe and effective. Collaboration is Key: One of the most exciting aspects of this program is how the different projects support and enhance each other. For example, a discovery in one project could lead to improvements in the others. This collaborative spirit means that success in any part of the program could have wide-reaching benefits, potentially leading to better treatments for a variety of childhood cancers. Inclusion of Minorities: At Texas Children's Hospital, we welcome children of all backgrounds for cell therapy studies. Over the past 5 years, of the 265 children treated, a diverse mix included 40.8% Hispanic; 11.3% Black, 6.4% Asian, 4% American Indian, and 0.4% Hawaiian, reflecting the population of Texas, and especially the Houston area. This shows our commitment to treating children from all communities. In Conclusion: This program represents a significant step forward in the fight against pediatric cancers that are currently difficult to cure. The investigators aim to develop new treatments as well as to understand more about how these treatments work, how we can improve them, and what side effects they might have. This research could pave the way for future advances in cancer therapy, ultimately benefiting both children and adults.

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