ROR2 as a candidate immunotherapeutic target in Wilms Tumor

Mentor Name: John Maris
Cancer immunotherapy is a promising field with curative potential for pediatric leukemias and emerging efficacy in pediatric solid tumors. Common approaches include antibody-drug conjugates (ADC), which deliver toxic payloads to cancer cells, and chimeric antigen receptor T-cell (CAR-T) therapies, which reengineer T-cells to target and destroy cancer cells. At the Children’s Hospital of Philadelphia, our lab is focused on developing precise immunotherapies for high-risk pediatric cancers. This project aims to address the unmet need for effective, less toxic treatments for Wilms Tumor, the most common renal tumor in children, particularly its anaplastic subtype, which has unfavorable histological features and poor prognosis. Building on prior work in neuroblastoma, we applied a proteogenomic approach to identify cell surface proteins as therapeutic targets in Wilms Tumor. Our analysis revealed that ROR2, previously studied in osteosarcoma, is also expressed in Wilms Tumor, though it has not been explored in this context. We will collaborate with Poul Sorensen’s lab in British Columbia, who developed a ROR2-ADC for osteosarcoma, and we are investigating its potential in Wilms Tumor. We will verify ROR2 expression in Wilms Tumor cell line models using flow cytometry and western blotting. We will genetically manipulate ROR2 (via shRNA, siRNA, or CRISPR) to evaluate its role in tumor growth and proliferation using live-cell imaging. If ROR2 is confirmed as a surface protein, we will test the ROR2-ADC’s efficacy through cytotoxicity and internalization assays. This project has the potential to translate ROR2-ADC into a novel therapeutic option for children with high-risk renal cancers, advancing the field of pediatric oncology.