Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 130, Issue 2, Pages 733-747Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI121127
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Funding
- NIH [CA23766, R21CA162002]
- Aubrey Fund
- Claire Tow Foundation
- Major Family Foundation
- Max Cure Foundation
- Richard Rick J. Eisemann Pediatric Research Fund
- Banbury Foundation
- Edith Robertson Foundation
- Larry Smead Foundation
- NCI Cancer Center Support Grant [P30 CA08748]
- Cycle for Survival
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology
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BACKGROUND. Adoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients. METHODS. We developed a third-party, allogeneic. off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation. RESULTS. EBV-CTLs did not induce significant toxicities. One patient developed grade I skin graft-versus-host disease. Complete remission (CR) or sustained partial remission (PR) was achieved in 68 degrees/s of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, one year overall survival was 88.9% and 81.8%, respectively. In addition, 3 of 5 recipients with POD after a first cycle who received EBV-CTLs from a different donor achieved CR or durable PR (60/0) and survived longer than 1 year. Maximal responses were achieved after a median of 2 cycles. CONCLUSION. Third-party EBV-CTLs of defined HLA restriction provide safe, immediately accessible treatment for EBV-PTLD. Secondary treatment with EBV-CTLs restricted by a different HLA allele (switch therapy) can also induce remissions if initial EBV-CTLs are ineffective. These results suggest a promising potential therapy for patients with rituximab-refractory EBV-associated lymphoma after transplantation.
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