{"doi":"10.1172/jci134915","title":"mRNA vaccine–induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer","abstract":"BACKGROUNDTherapeutic vaccinations against cancer have mainly targeted differentiation antigens, cancer-testis antigens, and overexpressed antigens and have thus far resulted in little clinical benefit. Studies conducted by multiple groups have demonstrated that T cells recognizing neoantigens are present in most cancers and offer a specific and highly immunogenic target for personalized vaccination.METHODSWe recently developed a process using tumor-infiltrating lymphocytes to identify the specific immunogenic mutations expressed in patients' tumors. Here, validated, defined neoantigens, predicted neoepitopes, and mutations of driver genes were concatenated into a single mRNA construct to vaccinate patients with metastatic gastrointestinal cancer.RESULTSThe vaccine was safe and elicited mutation-specific T cell responses against predicted neoepitopes not detected before vaccination. Furthermore, we were able to isolate and verify T cell receptors targeting KRASG12D mutation. We observed no objective clinical responses in the 4 patients treated in this trial.CONCLUSIONThis vaccine was safe, and potential future combination of such vaccines with checkpoint inhibitors or adoptive T cell therapy should be evaluated for possible clinical benefit in patients with common epithelial cancers.TRIAL REGISTRATIONPhase I/II protocol (NCT03480152) was approved by the IRB committee of the NIH and the FDA.FUNDINGCenter for Clinical Research, NCI, NIH.","journal":"Journal of Clinical Investigation","year":2020,"id":48440,"datarank":3.8326498184852573,"base_score":6.040254711277414,"endowment":6.040254711277414,"self_citation_contribution":0.9060382066916122,"citation_network_contribution":2.926611611793645,"self_endowment_contribution":0.9060382066916122,"citer_contribution":2.926611611793645,"corpus_percentile":null,"corpus_rank":null,"citation_count":419,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03480152"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":226275,"name":"Jared J. Gartner","orcid":"0000-0003-2924-3519","position":1,"is_corresponding":false},{"id":98421,"name":"Tal Zaks","orcid":null,"position":2,"is_corresponding":false},{"id":229915,"name":"Kristen Hopson","orcid":null,"position":3,"is_corresponding":false},{"id":228784,"name":"Noam Levin","orcid":"0000-0003-0664-2808","position":4,"is_corresponding":false},{"id":226278,"name":"Biman C. Paria","orcid":"0000-0002-8492-3448","position":5,"is_corresponding":false},{"id":226277,"name":"Maria R. Parkhurst","orcid":"0000-0001-7231-5069","position":6,"is_corresponding":false},{"id":229916,"name":"Rami Yossef","orcid":null,"position":7,"is_corresponding":false},{"id":226265,"name":"Frank J. Lowery","orcid":"0000-0002-4620-5293","position":8,"is_corresponding":false},{"id":229917,"name":"Mohammad Jafferji","orcid":null,"position":9,"is_corresponding":false},{"id":228785,"name":"Todd D. Prickett","orcid":"0000-0001-5466-4150","position":10,"is_corresponding":false},{"id":226281,"name":"Stephanie L. Goff","orcid":"0000-0003-3317-9804","position":11,"is_corresponding":false},{"id":229918,"name":"Christine T. McGowan","orcid":null,"position":12,"is_corresponding":false},{"id":228786,"name":"Samantha J. Seitter","orcid":"0000-0002-3193-8718","position":13,"is_corresponding":false},{"id":228787,"name":"Mackenzie L. Shindorf","orcid":"0000-0001-8638-9317","position":14,"is_corresponding":false},{"id":228788,"name":"Anup Y. Parikh","orcid":"0000-0002-1169-4568","position":15,"is_corresponding":false},{"id":228789,"name":"Praveen D. Chatani","orcid":"0000-0002-1765-214X","position":16,"is_corresponding":false},{"id":226282,"name":"Paul F. Robbins","orcid":"0000-0002-1260-8123","position":17,"is_corresponding":false},{"id":226283,"name":"Steven A. Rosenberg","orcid":"0000-0002-8939-8910","position":18,"is_corresponding":false},{"id":228783,"name":"Gal Cafri","orcid":"0000-0002-9427-0479","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-18T20:34:12.647743Z","pmid":"33016924","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":[]}