Nature communications, 2024-05, Vol.15 (1), p.3732-3732
2024
Details
- Autor(en) / Beteiligte
- Titel
- Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression
- Ist Teil von
- Nature communications, 2024-05, Vol.15 (1), p.3732-3732
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2024
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Immunotherapy with chimeric antigen receptor T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify cancer specific exon targets, here we analyze 1532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We find 2933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n = 148) or the alternatively spliced isoform (n = 9) level. Expression of selected alternatively spliced targets, including the EDB domain of fibronectin 1, and gene targets, such as COL11A1, are validated in pediatric patient derived xenograft tumors. We generate T cells expressing chimeric antigen receptors specific for the EDB domain or COL11A1 and demonstrate that these have antitumor activity. The full target list, explorable via an interactive web portal ( https://cseminer.stjude.org/ ), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 2041-1723DOI: 10.1038/s41467-024-47649-yTitel-ID: cdi_doaj_primary_oai_doaj_org_article_a7f623660f4c451a9230c9fee62ee7a1
- Format
- –
- Schlagworte
- Alternative Splicing, Animals, Anticancer properties, Antigens, Antitumor activity, Antitumour agents, Availability, Brain, Brain cancer, Brain Neoplasms - genetics, Brain Neoplasms - immunology, Brain Neoplasms - therapy, Brain tumors, Cancer, Cell Line, Tumor, Child, Chimeric antigen receptors, Datasets, Exons, Exons - genetics, Fibronectin, Fibronectins - genetics, Fibronectins - immunology, Fibronectins - metabolism, Gene Expression Regulation, Neoplastic, Humans, Immunotherapy, Immunotherapy - methods, Immunotherapy, Adoptive - methods, Lymphocytes, Lymphocytes T, Mice, Neoplasms, Pediatrics, Receptors, Receptors, Chimeric Antigen - genetics, Receptors, Chimeric Antigen - immunology, Receptors, Chimeric Antigen - metabolism, RNA-Seq, T-Lymphocytes - immunology, T-Lymphocytes - metabolism, Tumors, Workflow, Xenograft Model Antitumor Assays, Xenotransplantation