Validating novel CAR T cell targets in neuroblastoma
Mentor Name: Kristopher Bosse
Neuroblastoma is a cancer that occurs in young children and is often lethal. Though recent immunotherapeutic advances have resulted in enthusiasm for the use of this treatment, new molecules are needed to safely and specifically target neuroblastomas. Ideal immunotherapeutic targets should play a role in helping tumors grow, be located on the surface of and expressed robustly in tumor cells, and must not be present in normal tissues. We have previously discovered and researched molecules that meet these criteria, such as the protein glypican 2 (GPC2), but several other molecules meeting these criteria have remained unexplored in their immunotherapeutic potential, including the nicotinic acetylcholine receptor (nAChR) CHRNA3. This project will focus first on validating how CHRNA3/B4 heteropentamers in neuroblastoma contribute to a malignant phenotype. The project will then shift towards optimizing CHRNA3/B4 CAR T cells by testing if CAR constructs with a 4-1BB co-stimulatory domain enhance T cell proliferation and persistence.
