Development of a novel radiopharmaceutical agent for non-invasive immunotherapy target detection and CAR T combination therapy in neuroblastoma

Dr. Rosa Nguyen, M.D., Ph.D. – National Cancer Institute, NIH NCI Pediatric Oncology, Bethesda, MD

Neuroblastoma (NB) is a solid tumor in children. Children with disease that has spread to other organs still do poorly. Our lab has developed a CAR T therapy that uses the patient’s immune cells to combat NB. Our CAR T therapy detects a target called glypican 2 (GPC2) that is found in NB cells but not in most healthy tissues. Upon sensing and binding to GPC2, the CAR T-cells can kill NB. However, one challenge in CAR T therapy is that it is often unknown whether the patient’s tumor has the target at the time they receive CAR T therapy. To obtain this information, it is necessary to perform a biopsy which is invasive and can be challenging. No existing test can tell us how much of the target is found in the tumor. So, we propose to develop a radiotracer to do “immunoPET”. We will use an antibody called hCT3 which can bind to GPC2. hCT3 will be bound to zirconium (89Zr), which allows us to measure GPC2 levels in NB tumors and eventually identify patients who benefit the most from GPC2 CAR T therapy. We will also develop a modified version of this. Instead of zirconium (89Zr), we will attach hCT3 to actinium (225Ac). 225Ac-hCT3 can deposit radiation in the tumor, shrink it, and make it more sensitive to CAR T therapy as well. This may make CAR T therapy work better. To summarize, we will develop 89Zr-hCT3 to image immunotherapy targets without the need for invasive procedures and 225Ac-hCT3 to improve CAR T therapy. Our studies are designed to improve patient care and survival.