Rebecca Epperly, MD, MSCI

Cellular immunotherapies have been successful in treating some children with relapsed or refractory high-risk disease, specifically for those with certain types of blood cancers. However, these therapies have not yet elicited a consistent anti-tumor response in other types of cancers, including solid tumors. My clinical research focus is on translating cellular immunotherapy approaches to improve the long-term outcome of children with high-risk malignancies. Specifically, I am interested in expanding the use of CAR T-cell therapy to effectively treat pediatric solid tumors and improving the long-term durability of CAR T-cell therapy for children with B-cell acute lymphoblastic leukemia.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy is an emerging treatment strategy for pediatric relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). By specifically targeting the B–cell-specific transmembrane glycoprotein, CD19, this form of CAR T-cell therapy induces remission in many patients with high-risk B-ALL, but up to half of patients experience subsequent relapse without additional therapy. These therapies are also accompanied by acute toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), and the long-term effects of this therapy are less understood.

My work in the B-ALL space leverages strong collaborations with translational scientists and clinicians to design and implement novel CAR T cells aiming to reduce the risk of relapse. Additionally, we are leading multi-center studies to understand potential long-term effects and outcomes for children treated with CAR T-cell therapy. These results will help gather a more comprehensive understanding of the biology driving successful CAR T-cell therapy as well as uncover the mechanisms which can reduce the therapy’s efficacy. Ultimately, this information can be utilized to engineer next generation CAR T cells for use in the treatment of B-ALL, and inform the design and implementation of cellular therapy products for other types of pediatric cancers that have historically been resistant to CAR T-cell therapy.

Immunotherapies, such as CAR T-cell therapy, have had the biggest impact in the treatment of blood cancers, but this success has not yet translated to the treatment of pediatric solid tumors. Children with high-risk solid tumors have poor outcomes and, despite aggressive treatment strategies, survival rates remain low. My work focuses on understanding the challenges of using immunotherapy approaches to treat solid tumors and developing strategies to overcome these challenges.

One avenue we are exploring is using B7-H3-directed CAR T cells for pediatric solid tumors. B7-H3 is an immune regulatory protein that, compared to normal tissues, has increased expression on solid tumor tissues, especially for sarcomas. Although we have an attractive antigenic target, we must figure out how to get the engineered CAR T cells to effectively localize and penetrate the solid tumor, expand and persist. Other challenges include overcoming the harsh tumor microenvironment and intrinsic tumor resistance. As the leader of our solid tumor cellular therapy clinical efforts, I work with a team evaluating several approaches to address these barriers. These include designing combination therapy approaches, such as using radiation together with cellular immunotherapy, and positioning cellular therapy in the setting of low disease burden to determine if these multimodal strategies improve clinical response rates. We are also translating next-generation cellular therapy products for pediatric solid tumors which incorporate additional genetic modifications to improve T-cell fitness.

Dr. Epperly is a pediatric oncologist who received her medical degree from the University of Iowa. She completed a residency program focused on pediatrics at UPMC Children’s Hospital of Pittsburgh before coming to St. Jude for a pediatric hematology-oncology fellowship as well as a pediatric bone marrow transplant and cellular therapy fellowship. Dr. Epperly joined the St. Jude faculty as an instructor in 2021 and is currently an Assistant Member in the Department of Bone Marrow Transplantation & Cellular Therapy. In 2024, Dr. Epperly received a master’s degree in clinical investigations from the St. Jude Graduate School of Biomedical Sciences. Her clinical research focuses on expanding the reach of CAR T-cell therapy for pediatric patients. This includes both developing approaches to address unique challenges in solid tumors and improving long-term outcomes for children with B-ALL treated with CAR T-cell therapy. In addition, Dr. Epperly attends on the Bone Marrow Transplantation & Cellular Therapy clinical service and is actively engaged in mentoring and training the next generation of clinical fellows and clinical researchers.

Affiliations