학술논문
Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant
Document Type
article
Author
Susan E. Prockop; Aisha Hasan; Ekaterina Doubrovina; Parastoo B. Dahi; Irene Rodriguez-Sanchez; Michael Curry; Audrey Mauguen; Genovefa A. Papanicolaou; Yiqi Su; JinJuan Yao; Maria Arcila; Farid Boulad; Hugo Castro-Malaspina; Christina Cho; Kevin J. Curran; Sergio Giralt; Nancy A. Kernan; Guenther Koehne; Ann Jakubowski; Esperanza Papadopoulos; Miguel-Angel Perales; Ioannis Politikos; Keith Price; Annamalai Selvakumar; Craig S. Sauter; Roni Tamari; Teresa Vizconde; James W. Young; Richard J. O’Reilly
Source
The Journal of Clinical Investigation, Vol 133, Iss 10 (2023)
Subject
Language
English
ISSN
1558-8238
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.