title: Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation.
abstract: Donor lymphocyte infusion (DLI), a standard relapse treatment after allogeneic stem cell transplantation (AlloSCT), has limited efficacy and often triggers GVHD. We hypothesized that after AlloSCT tumor-infiltrating donor lymphocytes could be costimulated ex vivo to preferentially activate/expand antitumor effectors. We tested the feasibility and safety of costimulated, tumor-derived donor lymphocyte (TDL) infusion in a phase 1 trial. Tumor was resected from 8 patients with B-cell malignancy progression post-AlloSCT; tumor cell suspensions were costimulated with anti-CD3/anti-CD28 Ab-coated magnetic beads and cultured to generate TDL products for each patient. Costimulation yielded increased proportions of T-bet(+)FoxP3(-) type 1 effector donor T cells. A median of 2.04 × 10(7) TDL/kg was infused; TDLs were well tolerated, notably without GVHD. Two transient positron emission tomography (PET) responses and 2 mixed responses were observed in these refractory tumors. TDL are a feasible, tolerable, and novel donor cell therapy alternative for relapse after AlloSCT.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892-1203, USA. hardyn@mail.nih.gov
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hardy
authors.forename: Vicki
authors.initials: V
authors.lastname: Fellowes
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Rose
authors.forename: Jeanne
authors.initials: J
authors.lastname: Odom
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Bazetta
authors.initials: B
authors.lastname: Blacklock-Schuver
authors.forename: Daniele N
authors.initials: DN
authors.lastname: Avila
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Memon
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Kurlander
authors.forename: Hahn M
authors.initials: HM
authors.lastname: Khuu
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Esther
authors.initials: E
authors.lastname: Mena
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwyer
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Ran
authors.initials: R
authors.lastname: Reshef
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Frances T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop
mesh_terms: D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006689:Hodgkin Disease / Q000601:surgery*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000601:surgery*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000637:transplantation*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000601:surgery*; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D014184:Transplantation, Homologous