Synapse - Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation

Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation Journal Article

Authors:	Prockop, S.; Doubrovina, E.; Suser, S.; Heller, G.; Barker, J.; Dahi, P.; Perales, M. A.; Papadopoulos, E.; Sauter, C.; Castro-Malaspina, H.; Boulad, F.; Curran, K. J.; Giralt, S.; Gyurkocza, B.; Hsu, K. C.; Jakubowski, A.; Hanash, A. M.; Kernan, N. A.; Kobos, R.; Koehne, G.; Landau, H.; Ponce, D.; Spitzer, B.; Young, J. W.; Behr, G.; Dunphy, M.; Haque, S.; Teruya-Feldstein, J.; Arcila, M.; Moung, C.; Hsu, S.; Hasan, A.; O'Reilly, R. J.
Article Title:	Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation
Abstract:	BACKGROUND. Adoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBVassociated 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% 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%) 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 EBVassociated lymphoma after transplantation. © 2020, American Society for Clinical Investigation.
Keywords:	adult; clinical article; treatment response; young adult; human cell; overall survival; clinical feature; histopathology; rituximab; cd3 antigen; cd8 antigen; t lymphocyte; disease association; cancer immunotherapy; multiple cycle treatment; phase 2 clinical trial; cohort analysis; cancer regression; acute graft versus host disease; cytotoxic t lymphocyte; lymphoma; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; natural killer cell; adoptive transfer; cd4 antigen; immunosuppressive treatment; hla a antigen; hla b antigen; tacrolimus; rapamycin; skin graft; cell mediated cytotoxicity; organ transplantation; epstein barr virus infection; killer cell; human; male; female; priority journal; article; tablecleucel
Journal Title:	Journal of Clinical Investigation
Volume:	130
Issue:	2
ISSN:	0021-9738
Publisher:	American Society for Clinical Investigation
Date Published:	2020-02-03
Start Page:	733
End Page:	747
Language:	English
DOI:	10.1172/jci121127
PUBMED:	31689242
PROVIDER:	scopus
PMCID:	PMC6994129
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078869931&doi=10.1172%2fJCI121127&partnerID=40&md5=c14cb9faeb65acbdff140aecc40a4a57
Notes:	Article -- Export Date: 2 March 2020 -- Source: Scopus