Cancer Immunology, Immunotherapy

, Volume 59, Issue 11, pp 1739–1744

Allogeneic natural killer cells for refractory lymphoma

Authors

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

DOI: 10.1007/s00262-010-0896-z

Cite this article as:
Bachanova, V., Burns, L.J., McKenna, D.H. et al. Cancer Immunol Immunother (2010) 59: 1739. doi:10.1007/s00262-010-0896-z

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 cellsAdoptive cell therapyLymphoma

Copyright information

© Springer-Verlag 2010