title: Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.
abstract: Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX;
authors.forename: Conrad Russell Y
authors.initials: CR
authors.lastname: Cruz
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Micklethwaite
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Ramos
authors.forename: Sharon
authors.initials: S
authors.lastname: Lam
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ku
authors.forename: Oumar
authors.initials: O
authors.lastname: Diouf
authors.forename: Enli
authors.initials: E
authors.lastname: Liu
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.forename: Sawa
authors.initials: S
authors.lastname: Ito
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.forename: Rammurti T
authors.initials: RT
authors.lastname: Kamble
authors.forename: George
authors.initials: G
authors.lastname: Carrum
authors.forename: Chitra M
authors.initials: CM
authors.lastname: Hosing
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Zhuyong
authors.initials: Z
authors.lastname: Mei
authors.forename: Bambi J
authors.initials: BJ
authors.lastname: Grilley
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000328:Adult; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002648:Child; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D015202:Protein Engineering; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation* / Q000821:virology; D014184:Transplantation, Homologous
chemical_list: D018941:Antigens, CD19; D000970:Antineoplastic Agents
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