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

摘要

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, butitisunknown whether allogeneic CD19.CARTcells 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 werenoinfusion-relatedtoxicities. VSTs persistedforamedianof8weeksinbloodand up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapseddiseaseduring the periodofCD19.CAR-VST persistence, whereas2patientswho received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation,donor CD19.CAR-VSTsexpanded concomitantlywithVSTs. HenceCD19.CAR-VSTsdisplayantitumoractivityand,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 ishigher)or planned vaccination with viral antigens may enhance disease control.