Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant
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-pa...
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-05-01
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| Series: | The Journal of Clinical Investigation |
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| Online Access: | https://doi.org/10.1172/JCI165476 |
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| 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 |
| author_facet | 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 |
| author_sort | Susan E. Prockop |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:09:08Z |
| format | Article |
| id | doaj.art-c8bff7f8a061422b8ccb6a5d37b43f5a |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:09:08Z |
| publishDate | 2023-05-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-c8bff7f8a061422b8ccb6a5d37b43f5a2023-11-07T16:20:20ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-05-0113310Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplantSusan E. ProckopAisha HasanEkaterina DoubrovinaParastoo B. DahiIrene Rodriguez-SanchezMichael CurryAudrey MauguenGenovefa A. PapanicolaouYiqi SuJinJuan YaoMaria ArcilaFarid BouladHugo Castro-MalaspinaChristina ChoKevin J. CurranSergio GiraltNancy A. KernanGuenther KoehneAnn JakubowskiEsperanza PapadopoulosMiguel-Angel PeralesIoannis PolitikosKeith PriceAnnamalai SelvakumarCraig S. SauterRoni TamariTeresa VizcondeJames W. YoungRichard J. O’ReillyBackground 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.https://doi.org/10.1172/JCI165476Infectious diseaseTransplantation |
| spellingShingle | 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 Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant The Journal of Clinical Investigation Infectious disease Transplantation |
| title | Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant |
| title_full | Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant |
| title_fullStr | Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant |
| title_full_unstemmed | Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant |
| title_short | Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant |
| title_sort | third party cytomegalovirus specific t cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant |
| topic | Infectious disease Transplantation |
| url | https://doi.org/10.1172/JCI165476 |
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