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.

• Authors: 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-Schuver, Bipulendu Jena, Michael R Bishop, Ronald E Gress, Steven A Rosenberg
• Journal: Blood (Blood) Vol. 122 Issue 25 Pg. 4129-39 (Dec 12 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 24055823 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Intramural)

Chemical References

• Antigens, CD19
• Receptors, Antigen, T-Cell
• Recombinant Fusion Proteins

Topics

• Adult
• Aged
• Allografts
• Antigens, CD19
• Female
• Humans
• Lymphocyte Transfusion
• Lymphoma, B-Cell (metabolism, therapy)
• Male
• Middle Aged
• Receptors, Antigen, T-Cell (biosynthesis)
• Recombinant Fusion Proteins (biosynthesis)
• Stem Cell Transplantation
• T-Lymphocytes (metabolism, transplantation)
• Tumor Lysis Syndrome (etiology, therapy)