title: Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19.
abstract: 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.
authors.affiliation: Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. kochendj@mail.nih.gov
authors.forename: James N
authors.initials: JN
authors.lastname: Kochenderfer
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Feldman
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Debbie-Ann N
authors.initials: DA
authors.lastname: Nathan
authors.forename: Brock J
authors.initials: BJ
authors.lastname: Lanier
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: 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
chemical_list: D018941:Antigens, CD19; D011946:Receptors, Antigen