{"doi":"10.1016/j.celrep.2025.116359","title":"Targeting an essential viral oncoprotein with an IL-7-enhanced mRNA vaccine induces durable immunity to Merkel cell carcinoma","abstract":"Although mRNA technologies have reinvigorated cancer vaccine development, the identification of strong antigens with consistent tumor cell expression and generation of durable antigen-specific CD8 + T cell memory remain key challenges. We identified the Merkel cell carcinoma (MCC) large T antigen (LTA) as an optimal vaccine target, essential for tumor cell survival and immunogenic in a cancer with high unmet clinical need. We developed an mRNA vaccine to MCC-LTA in murine studies and patient samples. We showed that antigen loss develops rapidly and causes resistance in mouse models when immunogenic, but non-essential antigens are targeted. To improve T cell response durability, we co-encoded LTA and IL-7, co-localizing proliferative and memory signals spatially and temporally with antigen exposure. IL-7-containing mRNA vaccines improved antigen-specific T cell expansion, memory differentiation, and tumor control. We propose that the principles of antigen essentiality and memory signal co-encoding may be adapted to improve the efficacy of mRNA therapeutics.","journal":"Cell Reports","year":2025,"id":547333,"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":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1023585,"name":"Kathryn Clulo","orcid":null,"position":1,"is_corresponding":false},{"id":1440183,"name":"Yuewei Fei","orcid":null,"position":2,"is_corresponding":false},{"id":917465,"name":"Therese Cordero Dumit","orcid":"0000-0003-2406-0350","position":3,"is_corresponding":false},{"id":1372583,"name":"Frankie Scallo","orcid":null,"position":4,"is_corresponding":false},{"id":1440184,"name":"Jerry William Allen","orcid":null,"position":5,"is_corresponding":false},{"id":241193,"name":"Emily Chang","orcid":"0000-0001-5126-1698","position":6,"is_corresponding":false},{"id":1022577,"name":"Curtis J. Perry","orcid":"0000-0003-3715-5332","position":7,"is_corresponding":false},{"id":1363209,"name":"Lena V. Wirth","orcid":"0000-0001-7776-2853","position":8,"is_corresponding":false},{"id":1439773,"name":"Daniel A. Jacobs","orcid":"0000-0002-6267-9827","position":9,"is_corresponding":false},{"id":16392,"name":"David A. Braun","orcid":"0000-0003-4543-5553","position":10,"is_corresponding":false},{"id":13279,"name":"Marcus Bosenberg","orcid":"0000-0003-0166-1612","position":11,"is_corresponding":false},{"id":226316,"name":"Thuy Tran","orcid":"0000-0002-6244-7575","position":12,"is_corresponding":false},{"id":291535,"name":"James Clune","orcid":"0000-0002-2398-4634","position":13,"is_corresponding":false},{"id":226323,"name":"Harriet M. Kluger","orcid":"0000-0002-4932-9873","position":14,"is_corresponding":false},{"id":291534,"name":"Kelly Olino","orcid":"0000-0001-6209-5218","position":15,"is_corresponding":false},{"id":322577,"name":"Jeffrey J. Ishizuka","orcid":"0000-0002-4271-7312","position":16,"is_corresponding":false},{"id":1023443,"name":"Alexander Frey","orcid":null,"position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:53:41.314800Z","pmid":"41042672","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":[]}