@article{10.1172/JCI165476, author = {Susan E. Prockop AND Aisha Hasan AND Ekaterina Doubrovina AND Parastoo B. Dahi AND Irene Rodriguez-Sanchez AND Michael Curry AND Audrey Mauguen AND Genovefa A. Papanicolaou AND Yiqi Su AND JinJuan Yao AND Maria Arcila AND Farid Boulad AND Hugo Castro-Malaspina AND Christina Cho AND Kevin J. Curran AND Sergio Giralt AND Nancy A. Kernan AND Guenther Koehne AND Ann Jakubowski AND Esperanza Papadopoulos AND Miguel-Angel Perales AND Ioannis Politikos AND Keith Price AND Annamalai Selvakumar AND Craig S. Sauter AND Roni Tamari AND Teresa Vizconde AND James W. Young AND Richard J. O’Reilly}, journal = {The Journal of Clinical Investigation}, publisher = {The American Society for Clinical Investigation}, title = {Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant}, year = {2023}, month = {5}, volume = {133}, url = {https://www.jci.org/articles/view/165476}, abstract = {Background Refractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).Methods In 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.Results T cell infusions were well tolerated. Of 59 subjects evaluable for response, 38 (64%) achieved complete or durable partial responses.Conclusions Recipients 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 Registration NCT00674648; NCT01646645; NCT02136797 (NIH).Funding NIH (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.}, number = {10}, doi = {10.1172/JCI165476}, url = {https://doi.org/10.1172/JCI165476}, }