{"doi":"10.1172/jci165476","title":"Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant","abstract":"BackgroundRefractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).MethodsIn phase I/II trials, we treated 67 subjects for CMV viremia or disease arising after HCT with adoptive transfer of banked, third-party, CMVpp65-sensitized T cells (CMVpp65-VSTs). All were evaluable for toxicity and 59 for response. Evaluable subjects had CMV disease or persisting viremia that had failed at least 2 weeks of induction therapy with a median of 3 antiviral drugs; 84.7% had more than 3 of 11 high-risk features. CMVpp65-VSTs were specific for 1 to 3 CMVpp65 epitopes, presented by a limited set of HLA class I or II alleles, and were selected based on high-resolution HLA matching at 2 of 10 HLA alleles and matching for subject and subject's HCT donor for 1 or more alleles through which the CMVpp65-VSTs were restricted.ResultsT cell infusions were well tolerated. Of 59 subjects evaluable for response, 38 (64%) achieved complete or durable partial responses.ConclusionsRecipients responding to CMVpp65VSTs experienced an improved overall survival. Of the risk factors evaluated, transplant type, recipient CD4+ and CD8+ T cell levels prior to adoptive therapy, and the HLA restriction of CMVpp65-VSTs infused each significantly affected responses. In addition, CMVpp65-specific T cells of HCT donor or recipient origin contributed to the durability of both complete and partial responses.Trial RegistrationNCT00674648; NCT01646645; NCT02136797 (NIH).FundingNIH (P01 CA23766, R21 CA162002 and P30 CA008748); Aubrey Fund; Claire Tow Foundation; Major Family Foundation; \"Rick\" Eisemann Pediatric Research Fund; Banbury Foundation; Edith Robertson Foundation; Larry Smead Foundation.","journal":"Journal of Clinical Investigation","year":2023,"id":319463,"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":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1028365,"name":"Aisha Hasan","orcid":"0000-0003-4540-6904","position":1,"is_corresponding":false},{"id":345814,"name":"Ekaterina Doubrovina","orcid":"0000-0002-2458-8692","position":2,"is_corresponding":false},{"id":237600,"name":"Parastoo B. 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Papadopoulos","orcid":"0000-0001-6066-1861","position":19,"is_corresponding":false},{"id":108873,"name":"Miguel‐Angel Perales","orcid":"0000-0002-5910-4571","position":20,"is_corresponding":false},{"id":108868,"name":"Ioannis Politikos","orcid":"0000-0002-2854-8751","position":21,"is_corresponding":false},{"id":1007386,"name":"K. Price","orcid":null,"position":22,"is_corresponding":false},{"id":346698,"name":"Annamalai Selvakumar","orcid":null,"position":23,"is_corresponding":false},{"id":237601,"name":"Craig S. Sauter","orcid":"0000-0002-5316-8785","position":24,"is_corresponding":false},{"id":268584,"name":"Roni Tamari","orcid":"0000-0002-2386-0850","position":25,"is_corresponding":false},{"id":345818,"name":"Teresa Vizconde","orcid":"0000-0003-1822-9383","position":26,"is_corresponding":false},{"id":352733,"name":"James W. Young","orcid":"0000-0002-0032-6559","position":27,"is_corresponding":false},{"id":327888,"name":"Richard J. 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