Synapse - Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant

Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant Journal Article

Authors:	Prockop, S. E.; Hasan, A.; Doubrovina, E.; Dahi, P. B.; Rodriguez-Sanchez, I.; Curry, M.; Mauguen, A.; Papanicolaou, G. A.; Su, Y.; Yao, J.; Arcila, M.; Boulad, F.; Castro-Malaspina, H.; Cho, C.; Curran, K. J.; Giralt, S.; Kernan, N. A.; Koehne, G.; Jakubowski, A.; Papadopoulos, E.; Perales, M. A.; Politikos, I.; Price, K.; Selvakumar, A.; Sauter, C. S.; Tamari, R.; Vizconde, T.; Young, J. W.; O'Reilly, R. J.
Article 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.
Keywords:	child; t cells; cd8+ t lymphocyte; cd8-positive t-lymphocytes; stem cell transplantation; hematopoietic stem cell transplantation; transplantation; immunotherapy; cytomegalovirus infection; cytomegalovirus; infectious disease; viremia; cytomegalovirus infections; humans; human
Journal Title:	Journal of Clinical Investigation
Volume:	133
Issue:	10
ISSN:	0021-9738
Publisher:	American Society for Clinical Investigation
Date Published:	2023-05-15
Start Page:	e165476
Language:	English
DOI:	10.1172/jci165476
PUBMED:	36951958
PROVIDER:	scopus
PMCID:	PMC10178844
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159735901&doi=10.1172%2fJCI165476&partnerID=40&md5=7718dfc1c224ab99ff1e6cbf9c0ab46e
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed (via Conflict of Interest statement) and PDF -- MSK corresponding author is Richard O'Reilly -- Export Date: 1 June 2023 -- Source: Scopus