Dendritic cell immunotherapy in non-small cell lung cancer

Abstract

14013 Background: Therapeutic outcomes of definitively treated non-small cell lung cancer (NSCLC) are very poor. In the past two decades, adoptive immunotherapy, based on tumor-infiltrating lymphocytes or lymphokine-activated killer cells, has been used in clinical trials. Dendritic cells (DCs) are highly specialized immune cells derived from bone marrow stem cells which are unique in their ability to initiate and maintain primary immune responses. The purpose of this trial is to decide dosage and to evaluate the clinical efficacy, immune responses, and safety by injecting dendritic cell vaccine in non-small cell lung cancer. Methods: In this clinical trial, maximum tolerated dose (MTD) was decided through the three step evaluations by initially injecting 3, 6, 12 X 106 autologous dendritic cells into the dermis for 3 times per 2 weeks and later 2 more times monthly in NSCLC. Enroll patients had completely standard therapy. Autologous dendritic cells were manipulated using GM-CSF and IL-4 for maturation and tumor lysate was loaded to DC by electroporation, pulse, or combination of both. Results: A total of 15 patients were enrolled from January 2004 to April 2006, and they were vaccinated with autologous tumor-lysate- pulsed monocyte-derived DCs. the maximum dosage of 12X106 cell decided in this trial was safe. At the end of the clinical trial, the tumor estimation was conducted for 8 patients with 1 case of SD (12.5%) and 7 cases of PD (87.8%). To assess the potential to generate a tumor-specific immune response, an assay developed to determine intracellular IFN-γ production before and after vaccination. IFN-γ was examined in 9 patients. Immune responses were increased after 4th vaccination in 5 patients, all were more than 100% response rate. this response was not correlated to clinical outcome. Conclusions: MTD, 12×106 cell in this trial proved to be safe and the possibility of new treatment is suggested considering the fact that the patients in this trial were the ones who failed in the standard therapy or were not eligible for the therapy. No significant financial relationships to disclose.