Adoptive Immunotherapy of Lung Cancer Using ANK Cells

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Abstract

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.