Center of Excellence for Pediatric Immuno-Oncology

The Center of Excellence for Pediatric Immuno-Oncology (CEPIO) serves as the central hub to advance and coordinate cross-disciplinary studies in immuno-oncology across St. Jude basic and clinical Departments, Cores, and Centers. Co-led by Hongbo Chi, PhD,  Chair of the Department of Immunology, and Stephen Gottschalk, MD, Chair of the Department of Bone Marrow Transplantation and Cellular Therapy, CEPIO operates with support from, and in collaboration with, the Comprehensive Cancer Center.

The mission of CEPIO is to advance and coordinate interdisciplinary research in discovery and translational immuno-oncology to understand disease mechanisms, discover druggable targets and translate these findings into curative therapies for pediatric cancer. Our vision is to cure the incurable; to harness the power of the immune system to recognize and destroy cancer cells.

Immunotherapy has revolutionized how we treat children with cancer, infectious diseases and other disorders. It holds the promise to not only provide cures for currently ‘incurable’ pediatric cancers but also reduce long-term adverse effects compared to conventional therapies. For over 30 years, St. Jude investigators have significantly contributed to the field of immunotherapy.

Virus-specific T-cell therapy

In the 1990s, a team led by Cliona Rooney, PhD, Helen Heslop, MD, and Malcolm Brenner, MD, PhD, performed pioneering studies with Epstein-Barr virus (EBV)-specific T cells. For the first time ever, researchers demonstrated that EBV-specific T cells could be safely administered to humans, and that these cells prevented and eradicated EBV-positive lymphoma post-transplant. Since then, T cells have been developed to prevent or treat other viral infections. Based on these studies, investigators have also adapted the technology to develop cancer-specific T-cell therapies.

CAR T-cell therapy

The advent of clinical grade cellular engineering enabled the generation of T cells that are genetically modified to target cancer cells. To date, the most successful approach engineers T cells to express chimeric antigen receptors (CARs) that recognize proteins expressed on the cell surface of cancer cells. For example, the FDA-approved CAR T-cell product for pediatric acute lymphoblastic leukemia (ALL) uses a CAR that recognizes CD19, which was originally developed in the early 2000s by Dario Campana, MD, at St. Jude. In addition, Terrence Geiger, MD, PhD, now Deputy Director for Academic and Biomedical Operations, developed novel CARs for pediatric acute myeloid leukemia (AML). Since 2018, under the leadership of Stephen Gottschalk, MD, St. Jude has developed its own active clinical CAR T-cell therapy program, making St. Jude one of the first pediatric hospitals to provide this type of immunotherapy to patients. 

Currently, multiple St. Jude investigators are pioneering CAR T-cell therapy for a variety of tumor types: for hematological malignancies, Aimee Talleur, MD, Swati Naik, MD, and Paulina Velasquez, MD, all from the Department of Bone Marrow Transplantation & Cellular Therapy; for solid tumors, Rebecca Epperly, MD, and Christopher DeRenzo, MD, MBA, Department of Bone Marrow Transplantation & Cellular Therapy, and Lindsay Talbot, MD, Department of Surgery; for brain tumors, Kelsey Bertrand, MD, MSc, MBBS, FAAP, Department of Oncology, Giedre Krenciute, PhD, and Christopher DeRenzo, MD, Department of Bone Marrow Transplantation & Cellular Therapy. 

Next generation T-cell therapy

While T-cell therapy has been an effective treatment for ALL, it has been less successful for other cancers including AML, solid tumors and brain tumors. St. Jude investigators have focused on discovery-based research and novel engineering approaches to improve these therapies. 

In vivo CRISPR perturbation screens performed by the Chi lab identified negative regulators in T cells that limit their anti-tumor activity and Benjamin Youngblood, PhD, and Caitlin Zebley, MD, PhD, Department of Bone Marrow Transplantation & Cellular Therapy, deciphered epigenetic programs that limit T-cell function. St. Jude investigators are also actively exploring additional genetic modifications of T cells to enhance their activity against pediatric cancers. Together, these discoveries lay the foundation for the next generation of T-cell therapies that stand to increase cure rates and improve quality of life for patients. 

GD2 monoclonal antibodies

Over the last decade, Wayne Furman, MD, Sara Federico, MD, and Alberto Pappo, MD, Department of Oncology, developed a novel GD2 monoclonal antibody for patients with neuroblastoma and demonstrated its safety and efficacy in clinical studies. Work is being done to combine this antibody with an immune stimulatory cytokine to further improve its therapeutic efficacy.

The future of immunotherapy at St. Jude

Immunotherapy will play an integral role in changing the outlook for incurable and relapsed pediatric cancers. With already-established basic and translational immuno-oncology and immunotherapy-focused research programs and St. Jude’s continued recruitment of cellular immunotherapy experts, we are advancing our understanding of the landscape of target antigens associated with pediatric cancers. These findings will allow for the identification of attractive immunotherapeutic targets that researchers can leverage to engineer the next generation of CAR T cells. Emphasis will also be placed on understanding the molecular nuances of the immune microenvironment, details which can dramatically impact immunotherapeutic interventions.  

CEPIO is actively recruiting faculty and staff who are motivated to explore discovery and translational research focused on pediatric immuno-oncology.

Consistently ranked Top 10 in the U.S. in Pediatric Cancer, St. Jude Children's Research Hospital is the only NCI-designated Comprehensive Cancer Center devoted solely to children, and home to the Pediatric Cancer Genome Project. The St. Jude campus is a truly unique research environment, encompassing state-of-the-art High Performance Computing (HPC) facilities, world-leading oncology basic research, and outstanding Shared Resources and Core Facilities. The $412M Advanced Research Center, opened in 2021, doubles the campus’s research space and adds support for an additional 1,000 employees.