Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation

James N. Kochenderfer, Mark E. Dudley, Robert O. Carpenter, Sadik H. Kassim, Jeremy J. Rose, William G. Telford, Frances T. Hakim, David C. Halverson, Daniel H. Fowler, Nancy M. Hardy, Anthony R. Mato, Dennis D. Hickstein, Juan C. Gea-Banacloche, Steven Z. Pavletic, Claude Sportes, Irina Maric, Steven A. Feldman, Brenna G. Hansen, Jennifer S. Wilder, Bazetta Blacklock-SchuverBipulendu Jena, Michael R. Bishop, Ronald E. Gress, Steven A. Rosenberg

Research output: Contribution to journalArticle

308 Citations (Scopus)

Abstract

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. This trial was registered at www.clinicaltrials.

Original languageEnglish (US)
Pages (from-to)4129-4139
Number of pages11
JournalBlood
Volume122
Issue number25
DOIs
StatePublished - Dec 12 2013

Fingerprint

T-cells
Hematopoietic Stem Cell Transplantation
T-Cell Antigen Receptor
Stem cells
Lymphocytes
CD19 Antigens
Tissue Donors
T-Lymphocytes
Antigen Receptors
Grafts
Neoplasms
Cells
Chemotherapy
Toxicity
Tumors
Graft vs Host Disease
Blood
Genes
B-Lymphocytes
T-Cell Prolymphocytic Leukemia

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kochenderfer, J. N., Dudley, M. E., Carpenter, R. O., Kassim, S. H., Rose, J. J., Telford, W. G., ... Rosenberg, S. A. (2013). Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood, 122(25), 4129-4139. https://doi.org/10.1182/blood-2013-08-519413

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. / Kochenderfer, James N.; Dudley, Mark E.; Carpenter, Robert O.; Kassim, Sadik H.; Rose, Jeremy J.; Telford, William G.; Hakim, Frances T.; Halverson, David C.; Fowler, Daniel H.; Hardy, Nancy M.; Mato, Anthony R.; Hickstein, Dennis D.; Gea-Banacloche, Juan C.; Pavletic, Steven Z.; Sportes, Claude; Maric, Irina; Feldman, Steven A.; Hansen, Brenna G.; Wilder, Jennifer S.; Blacklock-Schuver, Bazetta; Jena, Bipulendu; Bishop, Michael R.; Gress, Ronald E.; Rosenberg, Steven A.

In: Blood, Vol. 122, No. 25, 12.12.2013, p. 4129-4139.

Research output: Contribution to journalArticle

Kochenderfer, JN, Dudley, ME, Carpenter, RO, Kassim, SH, Rose, JJ, Telford, WG, Hakim, FT, Halverson, DC, Fowler, DH, Hardy, NM, Mato, AR, Hickstein, DD, Gea-Banacloche, JC, Pavletic, SZ, Sportes, C, Maric, I, Feldman, SA, Hansen, BG, Wilder, JS, Blacklock-Schuver, B, Jena, B, Bishop, MR, Gress, RE & Rosenberg, SA 2013, 'Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation', Blood, vol. 122, no. 25, pp. 4129-4139. https://doi.org/10.1182/blood-2013-08-519413
Kochenderfer, James N. ; Dudley, Mark E. ; Carpenter, Robert O. ; Kassim, Sadik H. ; Rose, Jeremy J. ; Telford, William G. ; Hakim, Frances T. ; Halverson, David C. ; Fowler, Daniel H. ; Hardy, Nancy M. ; Mato, Anthony R. ; Hickstein, Dennis D. ; Gea-Banacloche, Juan C. ; Pavletic, Steven Z. ; Sportes, Claude ; Maric, Irina ; Feldman, Steven A. ; Hansen, Brenna G. ; Wilder, Jennifer S. ; Blacklock-Schuver, Bazetta ; Jena, Bipulendu ; Bishop, Michael R. ; Gress, Ronald E. ; Rosenberg, Steven A. / Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. In: Blood. 2013 ; Vol. 122, No. 25. pp. 4129-4139.
@article{0f03a8d7255943c6b1262e69aa5934b1,
title = "Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation",
abstract = "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. This trial was registered at www.clinicaltrials.",
author = "Kochenderfer, {James N.} and Dudley, {Mark E.} and Carpenter, {Robert O.} and Kassim, {Sadik H.} and Rose, {Jeremy J.} and Telford, {William G.} and Hakim, {Frances T.} and Halverson, {David C.} and Fowler, {Daniel H.} and Hardy, {Nancy M.} and Mato, {Anthony R.} and Hickstein, {Dennis D.} and Gea-Banacloche, {Juan C.} and Pavletic, {Steven Z.} and Claude Sportes and Irina Maric and Feldman, {Steven A.} and Hansen, {Brenna G.} and Wilder, {Jennifer S.} and Bazetta Blacklock-Schuver and Bipulendu Jena and Bishop, {Michael R.} and Gress, {Ronald E.} and Rosenberg, {Steven A.}",
year = "2013",
month = "12",
day = "12",
doi = "10.1182/blood-2013-08-519413",
language = "English (US)",
volume = "122",
pages = "4129--4139",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "25",

}

TY - JOUR

T1 - Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation

AU - Kochenderfer, James N.

AU - Dudley, Mark E.

AU - Carpenter, Robert O.

AU - Kassim, Sadik H.

AU - Rose, Jeremy J.

AU - Telford, William G.

AU - Hakim, Frances T.

AU - Halverson, David C.

AU - Fowler, Daniel H.

AU - Hardy, Nancy M.

AU - Mato, Anthony R.

AU - Hickstein, Dennis D.

AU - Gea-Banacloche, Juan C.

AU - Pavletic, Steven Z.

AU - Sportes, Claude

AU - Maric, Irina

AU - Feldman, Steven A.

AU - Hansen, Brenna G.

AU - Wilder, Jennifer S.

AU - Blacklock-Schuver, Bazetta

AU - Jena, Bipulendu

AU - Bishop, Michael R.

AU - Gress, Ronald E.

AU - Rosenberg, Steven A.

PY - 2013/12/12

Y1 - 2013/12/12

N2 - 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. This trial was registered at www.clinicaltrials.

AB - 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. This trial was registered at www.clinicaltrials.

UR - http://www.scopus.com/inward/record.url?scp=84890827981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890827981&partnerID=8YFLogxK

U2 - 10.1182/blood-2013-08-519413

DO - 10.1182/blood-2013-08-519413

M3 - Article

C2 - 24055823

AN - SCOPUS:84890827981

VL - 122

SP - 4129

EP - 4139

JO - Blood

JF - Blood

SN - 0006-4971

IS - 25

ER -