TY - JOUR
T1 - Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed After allogeneic stem cell transplant
T2 - A phase 1 study
AU - Cruz, Conrad Russell Y.
AU - Micklethwaite, Kenneth P.
AU - Savoldo, Barbara
AU - Ramos, Carlos A.
AU - Lam, Sharon
AU - Ku, Stephanie
AU - Diouf, Oumar
AU - Liu, Enli
AU - Barrett, A. John
AU - Ito, Sawa
AU - Shpall, Elizabeth J.
AU - Krance, Robert A.
AU - Kamble, Rammurti T.
AU - Carrum, George
AU - Hosing, Chitra M.
AU - Gee, Adrian P.
AU - Mei, Zhuyong
AU - Grilley, Bambi J.
AU - Heslop, Helen E.
AU - Rooney, Cliona M.
AU - Brenner, Malcolm K.
AU - Bollard, Catherine M.
AU - Dotti, Gianpietro
PY - 2013/10/24
Y1 - 2013/10/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84887821770&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887821770&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-06-506741
DO - 10.1182/blood-2013-06-506741
M3 - Article
C2 - 24030379
AN - SCOPUS:84887821770
SN - 0006-4971
VL - 122
SP - 2956
EP - 2973
JO - Blood
JF - Blood
IS - 17
ER -