PROJECT SUMMARY Gliomas are heterogeneous brain tumors with capacity for malignant propagation, and no treatment options are curative. Our studies show that an uncharacteristic cancer testis antigen, SPDYE3 was found to be overexpressed in all subtypes as well as low- and high-grade gliomas, and its expression is associated a poor patient’s survival. Interestingly, SPDYE3 protein contains tandem repeat (TR) epitopes that have high binding affinity to predominant HLA haplotypes (HLA-A*02, HLA-A*01 and HLA-B*07), which makes this molecule a potential glioma target for TCR-based T cell therapy. In this proposed study, we will test our hypothesis that SPDYE3 is a novel glioma tumor antigen, which is involved in tumor progression. We anticipate translating our preclinical findings from this proposed study into a future clinical applications for patients with various stages of gliomas.