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Allogeneic natural killer cells for refractory lymphoma

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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.

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Acknowledgments

The clinical trial was supported in part by a gift from the patient advocate group, CLL Topics, Inc. The authors declare they have no conflict of interest. We would like to thank our dedicated research staff, nurse practitioner Megan Whitmore, research nurses Dixie Lewis and Roby Nicklow and clinical trial office staff, Jill Aughey, for their outstanding support and invaluable contributions in conducting the trial. We want to thank Michael Franklin and Carol Taubert for editorial assistance. We want to acknowledge the University of Minnesota Masonic Cancer Center Translational Therapy Core for their excellent assistance.

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  1. Blood and Marrow, Transplant Program, University of Minnesota, Mayo Mail Code 480, 420 Delaware Street SE, Minneapolis, MN, 55455, USA

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

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  1. Veronika Bachanova
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  2. Linda J. Burns
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  3. David H. McKenna
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  4. Julie Curtsinger
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  5. Angela Panoskaltsis-Mortari
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  7. Sarah Cooley
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  8. Daniel Weisdorf
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  9. Jeffrey S. Miller
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Correspondence to Veronika Bachanova.

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Bachanova, V., Burns, L.J., McKenna, D.H. et al. Allogeneic natural killer cells for refractory lymphoma. Cancer Immunol Immunother 59, 1739–1744 (2010). https://doi.org/10.1007/s00262-010-0896-z

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  • DOI: https://doi.org/10.1007/s00262-010-0896-z

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