Cancer Immunology, Immunotherapy

, Volume 59, Issue 11, pp 1739–1744 | Cite as

Allogeneic natural killer cells for refractory lymphoma

  • Veronika Bachanova
  • Linda J. Burns
  • David H. McKenna
  • Julie Curtsinger
  • Angela Panoskaltsis-Mortari
  • Bruce R. Lindgren
  • Sarah Cooley
  • Daniel Weisdorf
  • Jeffrey S. Miller
Short communication

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 × 106 units every other day × 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/µl vs. baseline: 58 ± 24 cells/µl, 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.

Keywords

Allogeneic NK cells Adoptive cell therapy Lymphoma 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Veronika Bachanova
    • 1
  • Linda J. Burns
    • 1
  • David H. McKenna
    • 1
  • Julie Curtsinger
    • 1
  • Angela Panoskaltsis-Mortari
    • 1
  • Bruce R. Lindgren
    • 1
  • Sarah Cooley
    • 1
  • Daniel Weisdorf
    • 1
  • Jeffrey S. Miller
    • 1
  1. 1.Blood and Marrow, Transplant ProgramUniversity of MinnesotaMinneapolisUSA

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