A combined immunopeptidomics, proteomics, and cell surface proteomics approach to identify immunotherapy targets for diffuse intrinsic pontine glioma

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Oncology, Vol 13 (2023)
Druh dokumentu: article
ISSN: 2234-943X
64829693
DOI: 10.3389/fonc.2023.1192448
Popis: IntroductionDiffuse 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.MethodsIn this study, a multi-omics approach was used to interrogate patient-derived DIPG cell lines and to identify potential targets for immunotherapy.ResultsThrough 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).DiscussionThe 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.
Databáze: Directory of Open Access Journals