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

3001 Background: HLA-mismatched NK cells have been found effective in acute myeloid leukemia pts. Preclinical studies revealed that activated NK cells massively infiltrate lung tissue and improve recipient survival, suggesting a potential role in lung cancer therapeutics. We performed this phase I trial to evaluate safety and antitumor responses of allogeneic, in vitro activated and expanded NK cells in combination with chemotherapy (C) in pts with advanced NSCLC. Methods: Pts with unresectable locally advanced/metastatic NSCLC receiving 1st/2nd line C were eligible. Two relative donors for each pt were selected based on their HLA and KIR typing. CD56 + cells were isolated from 150ml of donor peripheral blood and cultured for 20–23 days with 20ng/ml interleukin-15 and 10 -5 M hydrocortisone. Activated and expanded NK cells, after sterility, phenotype, and function testing, were diluted in 500ml N/S 0.9% with 2% human serum albumin and administered i.v. for 1 hour 2 days after previous and 1 week prior next C. Premedication with corticosteroids and/or H1 inhibitors was allowed. The number of NK cells to be injected was up to 2x10 11 /dose for up to 4 doses. Pts and donors signed detailed informed consent. Results: Between 11/2007 and 11/2008 16 pts (performance status 0–1) were enrolled; 1 pt had rapid disease progression before treatment. Pts characteristics: M/F 12/4; histology: adenocarcinoma/squamous cell carcinoma 13/3; stage IIIb/IV 2/14; 1 st /2 nd line treatment 13/3; median age 64 years (range, 50–71). The number of doses administered was 2 (N=9 pts), 3 (N=2 pts), or 4 (N=4 pts). The number of cells injected varied from 0.2–29x10 6 /Kg (mean 7.4x10 6 ±7.7x10 6 ). During and after injection of NK cells no side effect (local or systemic) was observed. With a median follow-up of 6 months (range, 1–14) 3 pts with partial response and 7 pts with disease stabilization were recorded. Conclusions: Adoptive transfer of allogeneic, in vitro activated and expanded NK cells in combination with chemotherapy is safe, even at the highest dose administered. Based on these encouraging results a randomized phase II trial is further justified. No significant financial relationships to disclose.