A Trial of Autologous Ex Vivo-Expanded NK Cell-Enriched Lymphocytes with Docetaxel in Patients with Advanced Non-Small Cell Lung Cancer As Second- or Third-Line Treatment: Phase IIa Study.

Background: New strategies are still needed to enhance the treatment outcome for advanced non-small cell lung cancer, in spite of recent remarkable developments. Cancer immunotherapy has been attractive since a long time, with diverse clinical attempts and results. In particular, natural killer (NK) cells have received considerable attention because of their potential role in immune surveillance in vivo by destroying infected or transformed cells. Major histocompatibility complex class I-related chain NB (MICA/B) on tumor cells, known as the representative ligand for NKG2D receptor on NK cells, has been reported to be modulated by a variety of stress factors, including some chemotherapeutic agents, and it is anticipated that enhancing MICA/B expression will be contributory to anticancer treatment. With recent development of expanding autologous ex vivo NK cell-enriched lymphocytes (NKL), we designed a trial to augment the anticancer effect by co-administering NKL and docetaxel, one of the second-line agents used for treatment of patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: Eligible patients were between the age of 20 and 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and previously received one chemotherapy or two regimens including one epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, stage histologically- or cytologically-proven NSCLC with measurable lesions. NKL were kindly prepared and provided from NKBIO Co. (Seongnam City, Korea). Feasibility, adverse effects, progression-free survival (PFS) were evaluated and compared with the historical control of weekly docetaxel regimen. Results: Nineteen patients were enrolled before early closure. NKL production and administration were feasible in all cases, even in those with disseminated disease. No additional adverse events were observed in addition to those reported for docetaxel-alone. PFS of 3 months and 105% response rate (RR), with two cases of partial response, were observed and were similar to the historical control (PFS=2.9 months, RR=8.0%). Conclusion: To our knowledge, this is the first report on the combination of NKL with docetaxel in patients with advanced NSCLC. Autologous NKL production and co-administration with docetaxel were feasible without further toxicity or complication. Benefit in PFS and RR, as compared with the historical control, was not detected in this study population with advanced NSCLC. In order to determine whether the combination of NKL and chemotherapy has any anticancer effect, an additional study should be performed in patients with low tumor burden, such as those with less advanced disease or those in remission.