From Ions to Immunotherapy: How a St. Jude Scientist Is Designing a CAR T-Cell Trial for Pediatric Brain Tumors
核心洞察
A St. Jude associate scientist is designing a first-in-human clinical trial for EPHA2 (搜索)-targeted CAR T cells in pediatric brain tumors including medulloblastoma (搜索).
The EPHA2 (搜索) protein is abnormally exposed on cancer cell surfaces while largely hidden in normal tissues, offering a potentially selective therapeutic target.
Preclinical models of medulloblastoma (搜索) have shown encouraging signs of activity, with safety evaluations underway before clinical translation.
An associate scientist at St. Jude Children's Research Hospital is charting an unconventional path from studying cobalt metal ions to designing a clinical trial for a novel CAR T-cell therapy targeting pediatric brain tumors. The work, conducted in the laboratory of Giedre Krenciute, PhD, in the Department of Bone Marrow Transplantation & Cellular Therapy, focuses on chimeric antigen receptor (CAR) T cells engineered to recognize EPHA2 (搜索), a protein that becomes abnormally exposed on the surface of cancer cells.
The researcher, who earned a PhD in chemistry from Northwestern University, joined St. Jude as a postdoctoral fellow with no prior background in immunotherapy. "I told her that I had no background in immunotherapy and that I did not aspire to run my own lab; instead, I wished to become someone's trusted right hand," the scientist recalled of the interview with Krenciute. Her response — "I can teach you anything if you're willing to learn" — set the tone for a career defined by cross-disciplinary learning.
Targeting EPHA2 (搜索) in Medulloblastoma (搜索)
The lab had previously investigated a CAR T cell targeting B7-H3 (搜索), a protein expressed on cancer cells but only a limited number of normal cells, allowing selective tumor destruction with reduced side effects. However, not every medulloblastoma (搜索) or other pediatric brain tumor expresses B7-H3, creating a therapeutic gap.
EPHA2 (搜索) emerged as a promising alternative target. In normal tissues, EPHA2 is largely sequestered within the structures that hold cells together. In cancer, however, this protein becomes abnormally exposed on the cell surface, making it more accessible to CAR T cells. "In preclinical models of medulloblastoma (搜索), we have seen encouraging signs of activity and are carefully evaluating safety," the researcher stated.
From Bench to Trial Design
Rather than publishing the preclinical findings and handing the project off to others for clinical development — the traditional path for a bench scientist — the researcher chose to remain involved in translational development. With support from Krenciute and Stephen Gottschalk, MD, chair of the Department of Bone Marrow Transplantation & Cellular Therapy, the scientist enrolled in the Clinical Investigations Master's Program at the St. Jude Graduate School of Biomedical Sciences.
The first year of the program covered fundamentals of clinical and epidemiological research. Now entering the second year, the scientist's thesis project involves designing the clinical trial for the EPHA2 (搜索)-directed CAR T-cell therapy for pediatric brain tumors, including medulloblastoma (搜索) — one of the most common malignant childhood brain cancers.
The Clinical Imperative
Medulloblastoma (搜索) presents a challenging treatment landscape. Many children respond well to initial therapy, but disease relapse remains largely lethal. Even when treatment succeeds, radiation and chemotherapy can leave lasting side effects. These realities drive the lab's focus on developing more precise, less toxic therapies.
The broader CAR T-cell research environment at St. Jude extends beyond brain tumors. Swati Naik, MBBS, also in the Department of Bone Marrow Transplantation and Cellular Therapy, advances CAR T-cell therapies for pediatric blood cancers, with a focus on acute myeloid leukemia (搜索). Naik, mentored by Gottschalk, works on refining CAR T-cell precision and effectiveness while developing transplantation approaches that combine graft engineering with immune effectors.
A Career Built on Learning
The defining feature of this research trajectory has been lifelong learning. "Scientists can sometimes feel locked into a particular field, thinking that the first subject they study determines everything that comes after. My experience has shown me otherwise," the researcher noted. "So much of science is learning how to learn, but once you do, you can apply it to anything."
The motivation is also deeply personal. Like many in cancer research, the scientist was shaped by an experience with the disease long before it became a profession: one of their closest friends lost a young sibling to cancer. "That loss has stayed with me. It is part of what gave me the resolve to keep stretching across disciplines and to continue pushing toward work that could one day help children and families facing a pediatric brain cancer."