SPDYE3, A Novel Cancer Testis (CT) Antigen for Glioma Immunotherapy

项目摘要 神经胶质瘤是一种异质性脑肿瘤，具有恶性增殖能力， 选择是治愈的。我们的研究表明，一种非特征性的癌睾丸抗原，SPDYE 3被发现， 在所有亚型以及低级别和高级别胶质瘤中均过表达，其表达与肿瘤的发生、发展和预后相关。 病人的生存率很低。有趣的是，SPDYE 3蛋白含有串联重复（TR）表位，其具有高的表位亲和力。 与主要HLA单倍型（HLA-A*02、HLA-A*01和HLA-B*07）的结合亲和力，这使得 分子是基于TCR的T细胞治疗的潜在胶质瘤靶点。 在这项拟议的研究中，我们将检验我们的假设，即SPDYE 3是一种新的胶质瘤肿瘤抗原， 与肿瘤进展有关我们期望将我们的临床前研究结果转化为 提出了一项未来临床应用于不同阶段神经胶质瘤患者的研究。

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.