Diffuse intrinsic pontine glioma (DIPG) is an almost universally fatal brain pediatric tumor and the only tumor indication where palliative radiotherapy is the current standard of care. Although chimeric antigen receptor (CAR) T-cell therapy may hold promise for treating DIPG, the elevated tumor heterogeneity and the prospect of antigen escape make the identification of additional targets crucial. Therefore, multiple targets need to be validated to facilitate a multipronged approach.