Center of Excellence for Pediatric Immuno-Oncology (CEPIO)

CEPIO will focus on the following research areas in pediatric immuno-oncology:

• Systems immunology: using multi-omics and systems approaches to understand how tumor cells interact with nonmalignant cells in the TME and decipher the immune landscape and immunosuppressive networks.
• Functional genomics: using functional genomics tools (e.g., CRISPR screening) to dissect mechanisms of tumor–immune interactions, discover druggable immuno-oncology targets, and develop combinatorial therapies.
• Translational immuno-oncology: optimizing cellular and genetic engineering strategies and translating discoveries into curative immunotherapies or combination therapies for pediatric cancer.

Immunotherapy has the potential to revolutionize 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 more than thirty years, St. Jude investigators have made significant contributions 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, PhD, MD, performed pioneering studies with Epstein-Barr virus (EBV)-specific T cells. They showed for the first time that EBV-specific T cells can be given safely to humans, and that these cells can prevent and eradicate 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 cell 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, 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, which uses FDA-approved CAR T cell products and those developed for investigator-initiated clinical studies. Currently, multiple St. Jude investigators are pioneering CAR T cell therapy for a variety of tumor types: Aimee Talleur, MD, Swati Naik, MD, and Paulina Velasquez, MD, for hematological malignancies; Rebecca Epperly, MD, Lindsay Talbot, MD, and Christopher DeRenzo, MD, for solid tumors; and Kelsey Bertrand, MD, Giedre Krenciute, PhD, and Christopher DeRenzo, MD, for brain tumors.

Next-generation T cell therapy

While T cell therapy has been very successful for ALL, it has been less successful for other cancers, including acute myeloid leukemia (AML), solid tumors and brain tumors. St. Jude investigators have therefore focused on discovery-based research and novel engineering approaches to improve these therapies. For example, Hongbo Chi, PhD, has identified negative regulators in T cells that limit their anti-tumor activity, by performing in vivo CRISPR perturbation screens. Benjamin Youngblood, PhD, and Caitlin Zebley, MD, PhD, have deciphered epigenetic programs that limit T cell function, and Paul Thomas, PhD, has identified T cell receptors that specifically recognize leukemias. Finally, St. Jude investigators are actively exploring additional genetic modifications of T cells to enhance their activity against pediatric cancers.

GD2 monoclonal antibodies

Over the last decade, Wayne Furman, MD, Sara Federico, MD, and Alberto Pappo, MD, have developed a novel GD2 monoclonal antibody for patients with neuroblastoma and demonstrated its safety and efficacy in clinical studies. Based on these encouraging results, a follow-up study will combine this antibody with an immune stimulatory cytokine to further improve its therapeutic efficacy.

Looking ahead

Through its current strategic plan, St. Jude has strengthened its cancer immunology and immunotherapy program. These includes recruitment of faculty with cellular immunotherapy expertise, including Julie Park, MD and Rebecca Gardner, MD, and the establishment of the Center of Excellence for Pediatric Immuno-Oncology (CEPIO) under the leadership of Hongbo Chi, PhD and Stephen Gottschalk, MD. 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.

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.