{"doi":"10.1101/2021.08.13.456263","title":"Proteogenomic Discovery of Neoantigens Facilitates Personalized Multi-antigen Targeted T cell Immunotherapy for Brain Tumors","abstract":"ABSTRACT Neoantigen discovery in pediatric brain tumors is hampered by their low mutational burden and scant tissue availability. We developed a low-input proteogenomic approach combining tumor DNA/RNA sequencing and mass spectrometry proteomics to identify tumor-restricted (neoantigen) peptides arising from multiple genomic aberrations to generate a highly target-specific, autologous, personalized T cell immunotherapy. Our data indicate that novel splice junctions are the primary source of neoantigens in medulloblastoma, a common pediatric brain tumor. Proteogenomically identified tumor-specific peptides are immunogenic and generate MHC II-based T cell responses. Moreover, polyclonal and polyfunctional T cells specific for tumor-specific peptides effectively eliminated tumor cells in vitro. Targeting novel tumor-specific antigens obviates the issue of central immune tolerance while potentially providing a safety margin favoring combination with other immune-activating therapies. These findings demonstrate the proteogenomic discovery of immunogenic tumor-specific peptides and lay the groundwork for personalized targeted T cell therapies for children with brain tumors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221498,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":87746,"name":"Melanie Grant","orcid":"0000-0002-5421-5889","position":1,"is_corresponding":false},{"id":822051,"name":"Aswini Panigrahi","orcid":null,"position":2,"is_corresponding":false},{"id":660647,"name":"Huizhen Zhang","orcid":"0000-0003-0520-1955","position":3,"is_corresponding":false},{"id":822052,"name":"Veronika Caisova","orcid":null,"position":4,"is_corresponding":false},{"id":263322,"name":"Catherine M. Bollard","orcid":"0000-0001-5140-9090","position":5,"is_corresponding":false},{"id":821570,"name":"Brian R. Rood","orcid":"0000-0003-3221-9421","position":6,"is_corresponding":false},{"id":232130,"name":"Samuel Rivero-Hinojosa","orcid":"0000-0002-3595-8273","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:53:55.215284Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}