Allogeneic natural killer cells for refractory lymphoma.
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.
Bachanova
Veronika
V
Blood and Marrow, Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA. bach0173@umn.edu
Burns
Linda J
LJ
McKenna
David H
DH
Curtsinger
Julie
J
Panoskaltsis-Mortari
Angela
A
Lindgren
Bruce R
BR
Cooley
Sarah
S
Weisdorf
Daniel
D
Miller
Jeffrey S
JS
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
D007376:Interleukin-2