title: Allogeneic natural killer cells for refractory lymphoma.
abstract: We reported that IL-2 activated autologous NK cells can induce, but not maintain durable remissions in lymphoma patients. We hypothesized that allogeneic NK cells may overcome class I MHC-mediated inhibition of NK cell killing. In a pilot study, we evaluated infusion of haploidentical donor NK cells for antitumor efficacy. Six patients with advanced B cell non-Hodgkin lymphoma (NHL) received rituximab, cyclophosphamide, and fludarabine as immunosupression to permit homeostatic NK cell expansion, followed by CD3-depleted NK cell-enriched cell products followed by subcutaneous IL-2 administration (10 x 10(6) units every other day x 6 doses). At 2 months, four patients showed an objective clinical response. We observed early donor cell persistence in two patients (blood and in tumor-bearing node), but this was not detectable beyond 7 days. All patients demonstrated substantial increases in host-regulatory T cells (Treg) after NK cell and IL-2 therapy (180 +/- 80 cells/microl vs. baseline: 58 +/- 24 cells/microl, p = 0.04) which may have limited donor cell expansion in vivo. These findings suggest safety and feasibility of allogeneic NK cell therapy in patients with lymphoma; however host Treg and inadequate immunodepletion may contribute to a hostile milieu for NK cell survival and expansion. Cell therapy trials should incorporate novel strategies to limit Treg expansion.
authors.affiliation: Blood and Marrow, Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA. bach0173@umn.edu
authors.forename: Veronika
authors.initials: V
authors.lastname: Bachanova
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Burns
authors.forename: David H
authors.initials: DH
authors.lastname: McKenna
authors.forename: Julie
authors.initials: J
authors.lastname: Curtsinger
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Lindgren
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000166:cytology / Q000637:transplantation*; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2