title: Clinical scale expansion of cytokine-induced killer cells is feasible from healthy donors and patients with acute and chronic myeloid leukemia at various stages of therapy.
abstract: OBJECTIVE
  In our clinical studies involving cytokine-induced killer (CIK) cells for patients with hematological malignancies, starting cells came from a heterogeneous group of patients and donors. Here we study the feasibility of expansion and analyzed the characteristics of the end product from starting cells derived from different sources and at different disease states.
  
  
  METHODS
  Seventy-five clinical scale cultures were grown from 28 patients and 20 donors in Good Manufacturing Practices facilities under CIK condition.
  
  
  RESULTS
  CIK cells could be successfully expanded from healthy donors, patients with acute myeloid leukemia recovering from chemotherapy, untreated patients with acute myeloid leukemia or myelodysplastic syndrome with circulating leukemic blasts, and patients with chronic myeloid leukemia on imatinib. Furthermore, CIK cells of donor origin could be expanded from leukapheresis product collected from patients who relapsed post-allogeneic transplantation, thereby offering a useful method of obtaining activated donor cells in patients for whom further donor cells were unavailable. Interestingly, CIK cells cultured from patients with untreated acute myeloid leukemia and myelodysplastic syndrome had a significantly higher proportion of CD3(+)CD56(+) subset and higher fold expansion of CD3(+) cells as compared to other groups of patients or healthy donors. Multivariate analysis showed that fresh starting cells expanded better than frozen-thawed cells, while prior exposure to granulocyte colony-stimulating factor or imatinib before harvesting did not adversely affect CIK cell expansion.
  
  
  CONCLUSIONS
  Clinical scale expansion of CIK cells is feasible from both healthy donors and leukemia patients at various stages of treatment. This robust system allows clinical translation using CIK cells as immunotherapy in various clinical settings.
authors.affiliation: Cell Therapy Facility, Health Sciences Authority, Singapore.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Niam
authors.forename: Yeh-Ching
authors.initials: YC
authors.lastname: Linn
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fook Chong
authors.forename: Tsyr-Jong
authors.initials: TJ
authors.lastname: Lim
authors.forename: Sixian
authors.initials: S
authors.lastname: Chu
authors.forename: Alicia
authors.initials: A
authors.lastname: Choong
authors.forename: Hao-Xiang
authors.initials: HX
authors.lastname: Yong
authors.forename: Garnet
authors.initials: G
authors.lastname: Suck
authors.forename: Marieta
authors.initials: M
authors.lastname: Chan
authors.forename: Mickey
authors.initials: M
authors.lastname: Koh
mesh_terms: D016022:Case-Control Studies; D055612:Cytokine-Induced Killer Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000601:surgery; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation