The Journal of Clinical Investigation (May 2023)

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

  • 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

Journal volume & issue
Vol. 133, no. 10

Abstract

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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.

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