{"doi":"10.1172/jci144195","title":"A therapeutic cancer vaccine delivers antigens and adjuvants to lymphoid tissues using genetically modified T cells","abstract":"Therapeutic vaccines that augment T cell responses to tumor antigens have been limited by poor potency in clinical trials. In contrast, the transfer of T cells modified with foreign transgenes frequently induces potent endogenous T cell responses to epitopes in the transgene product, and these responses are undesirable, because they lead to rejection of the transferred T cells. We sought to harness gene-modified T cells as a vaccine platform and developed cancer vaccines composed of autologous T cells modified with tumor antigens and additional adjuvant signals (Tvax). T cells expressing model antigens and a broad range of tumor neoantigens induced robust and durable T cell responses through cross-presentation of antigens by host DCs. Providing Tvax with signals such as CD80, CD137L, IFN-β, IL-12, GM-CSF, and FLT3L enhanced T cell priming. Coexpression of IL-12 and GM-CSF induced the strongest CD4+ and CD8+ T cell responses through complimentary effects on the recruitment and activation of DCs, mediated by autocrine IL-12 receptor signaling in the Tvax. Therapeutic vaccination with Tvax and adjuvants showed antitumor activity in subcutaneous and metastatic preclinical mouse models. Human T cells modified with neoantigens readily activated specific T cells derived from patients, providing a path for clinical translation of this therapeutic platform in cancer.","journal":"Journal of Clinical Investigation","year":2021,"id":170257,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"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":434373,"name":"Naina Singhi","orcid":"0000-0001-8431-1823","position":1,"is_corresponding":false},{"id":232687,"name":"Shivani Srivastava","orcid":"0000-0002-1626-8402","position":2,"is_corresponding":false},{"id":703019,"name":"Julia Szeto","orcid":null,"position":3,"is_corresponding":false},{"id":435117,"name":"Brenda L. Jesernig","orcid":null,"position":4,"is_corresponding":false},{"id":702427,"name":"Sylvia M. Stull","orcid":"0000-0002-9999-1531","position":5,"is_corresponding":false},{"id":646702,"name":"Matthew Fitzgibbon","orcid":"0009-0008-7557-0442","position":6,"is_corresponding":false},{"id":234472,"name":"Megha Sarvothama","orcid":null,"position":7,"is_corresponding":false},{"id":234473,"name":"Sushma Yechan-Gunja","orcid":null,"position":8,"is_corresponding":false},{"id":702428,"name":"Scott E. James","orcid":"0000-0002-3601-6819","position":9,"is_corresponding":false},{"id":232699,"name":"Stanley R. Riddell","orcid":"0000-0002-4688-9920","position":10,"is_corresponding":false},{"id":434372,"name":"Joshua Veatch","orcid":"0000-0002-6543-9255","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:46:19.728805Z","pmid":"34396986","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":[]}