一种综合的免疫肽组学、蛋白组学和细胞表面蛋白组学方法用于鉴定弥漫性鞍区胶质母细胞瘤免疫治疗靶点。
A combined immunopeptidomics, proteomics, and cell surface proteomics approach to identify immunotherapy targets for diffuse intrinsic pontine glioma.
发表日期：2023
作者：
Kirti Pandey, Stacie S Wang, Nicole A Mifsud, Pouya Faridi, Alexander J Davenport, Andrew I Webb, Jarrod J Sandow, Rochelle Ayala, Michelle Monje, Ryan S Cross, Sri H Ramarathinam, Misty R Jenkins, Anthony W Purcell
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
小脑桥池弥漫性胶质瘤(DIPG), 最近被重新分类为弥漫性中线胶质瘤亚型，是一种高度侵袭性的脑干肿瘤，影响着儿童和年轻成年人，无法治愈，中位生存期仅为9个月。传统治疗方法无效，突显了细胞免疫疗法等替代治疗策略的需求。然而，鉴定独特且特异的肿瘤细胞表面抗原以用于嵌合抗原受体（CAR）或T细胞受体（TCR）疗法的靶标是具有挑战性的。本研究采用多组学方法对来源于患者的DIPG细胞系进行了研究，并鉴定了潜在的免疫治疗靶点。通过免疫肽组学，鉴定到一系列可靶向的癌睾丸抗原和肿瘤相关抗原以及源自人类内源性逆转录病毒元素的肽抗原。蛋白质组学分析还显示了潜在药物靶点和细胞表面蛋白的上调，如受体簇27 (CD276)、B7同源物3蛋白（B7H3）、白细胞介素13α受体2（IL-13Rα2）、人表皮生长因子受体3（HER2），还有EphA2和EphA3两种类型A鞘蛋白受体。本研究的结果为科学界提供了一个宝贵的资源，以加速DIPG的免疫治疗方法。鉴定卡和TCR疗法的潜在靶点可能为治疗这种可怕疾病开辟新的途径。© 2023 Pandey, Wang, Mifsud, Faridi, Davenport, Webb, Sandow, Ayala, Monje, Cross, Ramarathinam, Jenkins and Purcell.
Diffuse intrinsic pontine glioma (DIPG), recently reclassified as a subtype of diffuse midline glioma, is a highly aggressive brainstem tumor affecting children and young adults, with no cure and a median survival of only 9 months. Conventional treatments are ineffective, highlighting the need for alternative therapeutic strategies such as cellular immunotherapy. However, identifying unique and tumor-specific cell surface antigens to target with chimeric antigen receptor (CAR) or T-cell receptor (TCR) therapies is challenging.In this study, a multi-omics approach was used to interrogate patient-derived DIPG cell lines and to identify potential targets for immunotherapy.Through immunopeptidomics, a range of targetable peptide antigens from cancer testis and tumor-associated antigens as well as peptides derived from human endogenous retroviral elements were identified. Proteomics analysis also revealed upregulation of potential drug targets and cell surface proteins such as Cluster of differentiation 27 (CD276) B7 homolog 3 protein (B7H3), Interleukin 13 alpha receptor 2 (IL-13Rα2), Human Epidermal Growth Factor Receptor 3 (HER2), Ephrin Type-A Receptor 2 (EphA2), and Ephrin Type-A Receptor 3 (EphA3).The results of this study provide a valuable resource for the scientific community to accelerate immunotherapeutic approaches for DIPG. Identifying potential targets for CAR and TCR therapies could open up new avenues for treating this devastating disease.Copyright © 2023 Pandey, Wang, Mifsud, Faridi, Davenport, Webb, Sandow, Ayala, Monje, Cross, Ramarathinam, Jenkins and Purcell.