title: Successful "in-flight" activation of natural killer cells during long-distance shipping.
abstract: BACKGROUND
  Natural killer (NK) cells have shown promise in the treatment of malignancy. However, the widespread use of these cells may be limited by both the lack of resources and the expertise needed to manufacture them and the apparent need to use only fresh cells. The NHLBI-sponsored Production Assistance for Cellular Therapies group was established to provide the resources and expertise to carry out cell therapy research, including support of clinical trials. Here we describe the qualification of in transit activation of an NK-cell therapy product in preparation for a Phase I clinical trial at a distant medical center.
  
  
  METHODS
  Nonmobilized apheresis mononuclear cell collections were CD3+ cell depleted, placed into culture bags with interleukin (IL)-2, and shipped from Minneapolis/Saint Paul, Minnesota, to Columbus, Ohio, and back to Minneapolis/Saint Paul, under warm, monitored temperatures. Products underwent quality control (QC) testing including cell count, immunophenotyping, viability, endotoxin, sterility culture, and cytotoxicity assays. One product tested the relative importance of IL-2 and controlled incubation.
  
  
  RESULTS
  The length of shipment ranged from 14 to 16 hours, and temperatures were well controlled. QC testing was acceptable based upon previous in-house experience. Controlled incubation was not necessary for successful activation of NK cells, but IL-2 appeared essential.
  
  
  CONCLUSIONS
  The need for novel cell therapies to be infused as fresh products may be a limitation for various cell types. However, we have shown that NK cells can be successfully shipped in the fresh state (allowing 48 hr from apheresis to product infusion) for use at clinical centers. Although IL-2 is critical for NK-cell activation, a 37 °C, 5% CO2 incubator is not.
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, St. Paul, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Koepsell
authors.forename: Diane M
authors.initials: DM
authors.lastname: Kadidlo
authors.forename: Susan
authors.initials: S
authors.lastname: Fautsch
authors.forename: Jeffrey
authors.initials: J
authors.lastname: McCullough
authors.forename: Hans
authors.initials: H
authors.lastname: Klingemann
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: David H
authors.initials: DH
authors.lastname: McKenna
mesh_terms: D001793:Blood Preservation / Q000379:methods; D017321:Clinical Trials, Phase I as Topic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D013997:Time Factors; D014195:Travel; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2