Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19.
Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti-CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.
Kochenderfer
James N
JN
Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. kochendj@mail.nih.gov
Wilson
Wyndham H
WH
Janik
John E
JE
Dudley
Mark E
ME
Stetler-Stevenson
Maryalice
M
Feldman
Steven A
SA
Maric
Irina
I
Raffeld
Mark
M
Nathan
Debbie-Ann N
DA
Lanier
Brock J
BJ
Morgan
Richard A
RA
Rosenberg
Steven A
SA
D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology*; D019070:Cell Lineage / Q000276:immunology*; D005818:Genetic Engineering; D006801:Humans; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D008297:Male; D011946:Receptors, Antigen / Q000276:immunology; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014161:Transduction, Genetic; D014182:Transplantation, Autologous
D018941:Antigens, CD19; D011946:Receptors, Antigen