Areas of Research Neuroblastoma

Neuroblastoma remains a therapeutic challenge and there is an urgent need for additional research to develop more effective and less toxic treatment options for children with this disease. We recognize that standard treatment options will not work for all children. Therefore, we are actively investigating new sequencing and genomic approaches to better characterize neuroblastic tumors.

Clinically, our program offers novel treatment options including Investigational New Drug (IND) trials, Children’s Oncology Group (COG) studies and local pilot clinical studies. Over the last decade, our translational program has become nationally recognized for the development and use of immunotherapy in patients with relapsed or refractory disease. We recently completed and published the largest trial using cGD2-specific chimeric antigen receptor T cells designed specifically for children with neuroblastoma.

Based on the biology and engineered properties of another white blood cell type, Natural Killer T cells, our center will enroll children with relapsed or refractory high-risk neuroblastoma on a first-in-man Phase I clinical trial. The study will test Natural Killer T cells genetically engineered to co-express a 2nd generation GD2-specific chimeric antigen receptor and interleukin-15 (a molecule which provides additional survival signal for Natural Killer T cells) and examine the safety of this therapy. In addtion, we will evaluate the expansion and persistence of infused Natural Killer T cells in children and measure their antitumor activity.

The neuroblastoma research program at Texas Children's Cancer Center is dedicated to laboratory and clinical research focused on increasing our understanding of neuroblastoma and developing new and more effective therapies. Our current research efforts focus on understanding the causes of neuroblastoma, identifying new targets for treatment, and evaluating the efficacy of new therapies. Neuroblastoma is the most common solid tumor in childhood and accounts for almost 10% of childhood cancers. While children with low- and intermediate-risk neuroblastoma have cure rates of over 90%, approximately 40% of children with neuroblastoma have "high-risk" tumors with much lower survival rates, despite aggressive treatment with combinations of chemotherapy, stem cell transplantation, surgery, and radiation therapy. Cases of "high-risk" neuroblastoma are also associated with frequent recurrences and tumors that are resistant to treatment. New treatments are needed for these children to improve the cure rates and reduce the occurrence and severity of the side effects of treatment.

Research is an ongoing priority for the Neuroblastoma Program at Texas Children's Cancer Center, and our doctors and scientists are continuously striving to translate laboratory discoveries into new treatments for children with neuroblastoma. Our current research efforts focus on understanding the causes of neuroblastoma, identifying new targets for treatment, and evaluating the efficacy of new therapies. Texas Children's Cancer Center has a large number of laboratories devoted to studying the causes of neuroblastoma and to developing new treatments that can be advanced into clinical trials for children with neuroblastoma.

Recent discoveries by Texas Children's Cancer Center scientists include:

• identification of novel microRNA's associated with aggressive neuroblastoma (Shohet et al 2011)
• identification of a novel set of circulating biomarkers associated with neuroblastoma (Egler et al 2011)
• identification of novel proteins involved in neuroblastoma resistance to chemotherapy (Shang et al 2010, Zage et al 2012)
• identification of a novel protein associated with neuroblastoma tumor cell growth (Vasudevan et al 2009)
• identification of novel immunotherapy and antiangiogenic treatment combinations effective against neuroblastoma (Louis et al 2011, Patterson et al 2011, Zage et al 2010)
• identification of a novel role for tumor-associated macrophages in the growth of neuroblastoma tumors (Liu et al 2012)

Future research by the scientists in the Neuroblastoma Program at Texas Children's Cancer Center will continue to explore new pathways, new targets, and new treatments in order to provide the most appropriate and most effective therapy for each and every child with neuroblastoma.