γδ T cells in combination with Newcastle disease virus and dendritic cell therapy as a novel immunotherapeutic approach in treating of advanced lung cancer.
ABSTRACT
Background: γδ T cells represent a minority white cell in blood, which expand dramatically in acute infections. γδ T cells recognize antigens usually in a non-MHC-restricted fashion. A number of trials have shown that epithelial tumors were susceptible to γδ T cell lysis. A combination of γδ T cells with other cell based immune therapies such as Newcastle disease virus (NDV) or dendritic cell therapy (DC) may enhance their therapeutic efficacy.
Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 200 ml whole blood for treatment of n=6 patients with advanced metastatic lung cancer. γδ T cells were expanded ex vivo with an amino –bisphosphonate (5 mM Zometa) and IL-2 (100 U/ml). After 10 to 12 days,γδ T cells were harvested by MACS techniques. Purity and activity were analyzed by flow cytometry. γδ T cells was administered to patients intravenously at monthly intervals. Additionally, patients receive a treatment with NDV and DC one day prior to the γδ T cell application.
Results: The mean percentage of γδ T cells within the isolated PBMC was 2.3%. After in-vitro expansion the mean percentage increased to 70% with expansion rates up to 268 fold. Further purification by MACS leads to a mean percentage of 92% (highest 99.6%). The mean number of infused γδ T cells was 3.82 x 108 for each treatment. Patients are 2-12 months under treatment to date. 2 patients had disease stabilization and are still alive (8 and 11 months). Another patient with bilateral SCLC and liver metastases showed a complete remission of the lung lesions and a remission of the liver metastases after two treatment cycles and is still alive (12 months).
Conclusions: γδ T cells can be efficiently expanded and purified. A combination of DC based therapy, NDV and treatment with γδ T cells may improve the clinical outcome for advanced lung cancer patients .