Small cell lung carcinoma (SCLC) is highly sensitive to chemoradiotherapy. Despite initial responses, however, relapses occur within a short time and 5 year survival rates remain poor. Activated natural killer (A-NK) cells are a subset of immune effector cells that can kill SCLC cell lines in vitro. The hypothesis that administration of A-NK cells following standard therapy for SCLC as adoptive immunotherapy will be safe and may provide a clinical benefit will be tested in 30 patients with limited or extensive stage disease. Patients with SCLC that have responded to standard therapy will receive autologous A-NK cells and a 4 day continuous infusion of low dose (2 X 10[6] IU/m2/d) IL-2. The primary aims of this study are to test the safety and toxicity of this regimen in patients with SCLC and the ability to generate A-NK cells of acceptable clinical quality following standard therapy for SCLC. Furthermore, a portion of the A-NK cells will be labeled with 111indium to examine the duration of time that adoptively transferred cells circulate in the blood and the localization of A-NK cells at sites of tumor. Secondary aims of the study include a comparison of overall survival and the time and site of disease progression in subjects who received A- NK cell immunotherapy versus a matched set of historical control patients. Clinical outcomes will be assessed for correlations with the quality of A-NK cells generated and the cytotoxic function of A-NK cells in vitro. Since no significant improvement in the management of patients with SCLC has occurred in the last two decades, adoptive immunotherapy using A-NK cells may offer a novel therapeutic approach in their treatment.
