title: T-cell therapy using a bank of EBV-specific cytotoxic T cells: lessons from a phase I/II feasibility and safety study.
abstract: We report herein the results we obtained and the limitations we experienced during the production and use of a bank of Epstein-Barr virus (EBV)-transformed human cytotoxic T lymphocytes (EBV-CTLs). To assess the feasibility and toxicity of this strategy, we selected and stored, in liquid nitrogen, 4 billion EBV-CTLs from each of the 13 selected donors. Subsequently, in a multicenter phase I/II study, 11 patients with EBV-associated lymphoma resistant to conventional treatments received 1-3 doses of 5 million EBV-CTLs/kg with 1-3 and 0-4 compatibilities for human leukocyte antigen (HLA)-I and HLA-II, respectively. Except for one event of fever after injection, no immediate or delayed toxicity, no graft versus host disease, and no graft rejection attributable to CTL infusion were observed. Three patients presented complete remission and 1 partial remission after treatment. Considering the clinical options currently available, and the constrains associated with CTL preparation and implementation, we conclude that CTL banks should consist of a reasonably small number of cell lines with documented specificities. This objective could be more easily achieved if the few homozygous donors for the most frequent HLA alleles of the targeted population could be made available for such a project.
authors.affiliation: *Inserm, U892 †CHU Nantes, Hôtel Dieu, UTCG ‡Etablissement Français du Sang (EFS), Pays de la Loire, Nantes §UMR 1098, EFS Bourgogne/Franche-Comté, Bourgogne/Franche-Comté ∥CHU Limoges, Limoges ¶CHU Bordeaux and University Bordeaux 2, Bordeaux #APHP Hôpital Pitié-Salpêtrière CHU Pitié Salpétrière **CHU Robert Debré §§Hôpital Saint-Antoine, Paris ††CHU Brest, Brest ‡‡CHU Lilles, Lille, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Gallot
authors.forename: Solène
authors.initials: S
authors.lastname: Vollant
authors.forename: Soraya
authors.initials: S
authors.lastname: Saïagh
authors.forename: Béatrice
authors.initials: B
authors.lastname: Clémenceau
authors.forename: Régine
authors.initials: R
authors.lastname: Vivien
authors.forename: Evelyne
authors.initials: E
authors.lastname: Cerato
authors.forename: Jean-D
authors.initials: JD
authors.lastname: Bignon
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.forename: Sylvain
authors.initials: S
authors.lastname: Choquet
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.forename: Irène
authors.initials: I
authors.lastname: Frachon
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Bruno
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mothy
authors.forename: Françoise
authors.initials: F
authors.lastname: Mechinaud
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Noël
authors.initials: N
authors.lastname: Milpied
authors.forename: Henri
authors.initials: H
authors.lastname: Vié
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002460:Cell Line; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D005240:Feasibility Studies; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D008223:Lymphoma / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult