Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation.
New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation (alloHSCT). We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. T cells for genetic modification were obtained from each patient's alloHSCT donor. All patients had malignancy that persisted after alloHSCT and standard donor lymphocyte infusions (DLIs). Patients did not receive chemotherapy prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions. The 10 treated patients received a single infusion of allogeneic anti-CD19-CAR T cells. Three patients had regressions of their malignancies. One patient with chronic lymphocytic leukemia (CLL) obtained an ongoing complete remission after treatment with allogeneic anti-CD19-CAR T cells, another CLL patient had tumor lysis syndrome as his leukemia dramatically regressed, and a patient with mantle cell lymphoma obtained an ongoing partial remission. None of the 10 patients developed graft-versus-host disease (GVHD). Toxicities included transient hypotension and fever. We detected cells containing the anti-CD19-CAR gene in the blood of 8 of 10 patients. These results show for the first time that donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to standard DLIs without causing GVHD.
Experimental Transplantation and Immunology Branch and.
James N
JN
Kochenderfer
Mark E
ME
Dudley
Robert O
RO
Carpenter
Sadik H
SH
Kassim
Jeremy J
JJ
Rose
William G
WG
Telford
Frances T
FT
Hakim
David C
DC
Halverson
Daniel H
DH
Fowler
Nancy M
NM
Hardy
Anthony R
AR
Mato
Dennis D
DD
Hickstein
Juan C
JC
Gea-Banacloche
Steven Z
SZ
Pavletic
Claude
C
Sportes
Irina
I
Maric
Steven A
SA
Feldman
Brenna G
BG
Hansen
Jennifer S
JS
Wilder
Bazetta
B
Blacklock-Schuver
Bipulendu
B
Jena
Michael R
MR
Bishop
Ronald E
RE
Gress
Steven A
SA
Rosenberg
D000328:Adult; D000368:Aged; D064591:Allografts; D018941:Antigens, CD19; D005260:Female; D006801:Humans; D017710:Lymphocyte Transfusion; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation*; D015275:Tumor Lysis Syndrome / Q000209:etiology / Q000628:therapy
D018941:Antigens, CD19; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins