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

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

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 × 10 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/μd 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.

Original languageEnglish (US)
Pages (from-to)1739-1744
Number of pages6
JournalCancer Immunology, Immunotherapy
Volume59
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • Adoptive cell therapy
  • Allogeneic NK cells
  • Lymphoma

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