Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study

CRY Cruz, KP Micklethwaite, B Savoldo… - Blood, The Journal …, 2013 - ashpublications.org
CRY Cruz, KP Micklethwaite, B Savoldo, CA Ramos, S Lam, S Ku, O Diouf, E Liu, AJ Barrett
Blood, The Journal of the American Society of Hematology, 2013ashpublications.org
Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19. CAR) are
active against B-cell malignancies, but it is unknown whether allogeneic CD19. CAR T cells
are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT),
infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and
display antiviral activity without inducing graft-vs-host disease; therefore, we determined
whether donor VSTs, engineered to express CD19. CAR, retained the characteristics of …
Abstract
Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control. This study is registered at clinicaltrials.gov as #NCT00840853.
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