MAGE3 and Survivin activated dendritic cell immunotherapy for the treatment of non-small cell lung cancer.

Abstract

Dendritic cell (DC) immunotherapy is an optimal cancer treatment, resulting in its emergence as a therapeutic choice; however, there are limited studies investigating dual antigen-pulsed DC immunotherapy in non-small cell lung cancer (NSCLC). In order to determine the effect of a recombinant melanoma-associated antigen (rMAGE-3) and recombinant Survivin (rSurvivin) peptide-pulsed DC immunotherapy in patients with NSCLC, the present clinical study was performed. DC immunotherapy was generated from the monocytes of patients with NSCLC and primed with rMAGE-3 and rSurvivin peptides. The present open-label, non-randomised study enrolled 16 patients with histologically confirmed stage I-IIIB NSCLC between December 2013 and October 2014. A prime immunotherapy (9.1×107 cells/dose) and a single boost (8.2×107 cells/dose) were administered 1 month apart intradermally and the patients were evaluated for immunological and clinical response. DC immunotherapy was well tolerated, with no serious adverse events. There was a single incidence of grade 1 fever, chills and fatigue. Out of the 16 patients enrolled, 11 patients showed stable disease and 5 showed disease progression. There was a significant increase in IFN-γ expression on day 60 vs. day 0 (P=0.048). An increasing trend in the mean cluster of differentiation (CD)4:CD8 values of day 30 and day 90 was observed, but this was not significant. The present study established that DCs primed with rMAGE-3 and rSurvivin may be used in NSCLC treatment. However, a larger study is required to address prominent issues, including secretion of immunosuppressive cytokines and mechanisms of tumour escape from immune surveillance. Several factors associated with the manufacturing and quality of immunotherapy also require standardisation.