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A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer

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Abstract

HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2–4 doses of activated NK cells from two relative donors. Donor’s CD56+ cells were cultured for 20–23 days with interleukin-15 (IL-15) and hydrocortisone (HC) and administered intravenously between chemotherapy cycles. Premedication with corticosteroids and/or H1 inhibitors was allowed. Sixteen patients (performance status 0–1) with adenocarcinoma (n = 13) or squamous cell carcinoma (n = 3) at stage IIIb (n = 5) or IV (n = 11) receiving 1st (n = 13) or 2nd (n = 3) line treatment were enrolled. Fifteen patients received 2–4 doses of allogeneic activated NK cells (0.2–29 × 106/kg/dose, median 4.15 × 106/kg/dose). No side effects (local or systemic) were observed. At a median 22-month follow-up (range, 16.5–26 months) 2 patients with partial response and 6 patients with disease stabilization were recorded. Median progression free survival and overall survival were 5.5 and 15 months, respectively. A 56% 1-year survival and a 19% 2-year survival were recorded. In conclusion, repetitive infusions of allogeneic, in vitro activated and expanded with IL-15/HC NK cells, in combination with chemotherapy are safe and potentially clinically effective.

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Acknowledgments

We are indebted to our patients and their relatives for their voluntary participation in this study as well as to the nurses at the Outpatient Unit of Saint Savas Cancer Hospital for taking care of patients. We also thank all the staff of the Biochemistry, the Microbiology, and the Hematology Departments of our Hospital for helping in the accomplishment of this trial and Ms Joanne Kalogeropoulou for excellent technical assistance. Supported by Regional Operational Program Attika no. 20 MIS code 59605 G.R. to M.P.

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Authors and Affiliations

  1. Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 171 Alexandras Avenue, 115 22, Athens, Greece

    Eleni G. Iliopoulou, Constantin N. Baxevanis, Michael Papamichail & Sonia A. Perez

  2. First Department of Medical Oncology, Saint Savas Cancer Hospital, Athens, Greece

    Panteleimon Kountourakis, Michalis V. Karamouzis, Dimitrios Doufexis, Alexandros Ardavanis & Gerasimos Rigatos

  3. Medical Oncology Department, Bank of Cyprus Oncology Centre, Nicosia, Cyprus

    Panteleimon Kountourakis

  4. Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece

    Michalis V. Karamouzis

Authors
  1. Eleni G. Iliopoulou
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Correspondence to Sonia A. Perez.

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Iliopoulou, E.G., Kountourakis, P., Karamouzis, M.V. et al. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother 59, 1781–1789 (2010). https://doi.org/10.1007/s00262-010-0904-3

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  • DOI: https://doi.org/10.1007/s00262-010-0904-3

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