Abstract 768: Lymphokine activated killer cell conditioned media induces monocytes to differentiate into a dendritic cell-like/activated monocyte phenotype with cytotoxic potential against glioblastoma

Abstract

Background: Despite advances in surgery and multimodal treatment regimens, Glioblastoma (GBM) continues to have poor overall survival outcomes and associated treatment morbidity. Cell-based immunotherapy is being explored as an option in the treatment of GBM. Treatment of GBM with lymphokine activated killer cells (LAK) generated by interleukin-2 (IL-2) stimulation has been associated with encouraging overall survival rates (Dillman RO et al. J Immunotherapy 2009 32:914-919). Since it has been reported that IL-2-activated lymphocytes can produce cytokines that may influence the differentiation and activation of monocytes (Kirsch M et al. J Neurooncol 1994 20:35-45), we explored the generation of activated monocytes and/or dendritic cells (DC) in LAK cell therapy products. Methods: Magnetic cell isolation of major histocompatibility complex II positive cells (HLA-DR) from LAK cell preparations revealed a small subpopulation of cells expressing CD80 and CD86 which also retained some CD14 expression. We then explored the possibility of generating activated monocytes and/or DC by incubating elutriated monocytes in the conditioned media of LAK cell preparations (LAK-CM) and examining their characteristics in comparison to standard GM-CSF/IL-4 DC or LAK cells. Results: The resulting LAK-CM incubated monocytes showed high levels of expression of CD80 (65.3%), CD86 (72.3%), HLA-DR (83.6%), comparable to the standard GM-CSF/IL-4 DC. The LAK-CM treated monocytes also retained their CD14 expression at (58.2% vs. 58.4%) and had similar levels of phagocytic ability compared to DC (14.7% vs. 12.7%) and demonstrated higher cytotoxicity levels against a model GBM cell line, U251, compared to either LAK cells themselves or the standard GM-CSF/IL-4 generated DC (85.6% vs. 55.9% vs. 60.9%, respectively). Conclusions: Combining lymphocytes and monocytes from elutriated lymphocyte fractions under LAK cell generation conditions (1000 IU/mL IL-2 in AIMV) also yielded similar dendritic cell/activated monocyte phenotypes suggesting that new combinations of cell therapy could be produced using this method with higher tumor cytotoxicity potentials as well as antigen cross presentation capabilities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 768. doi:10.1158/1538-7445.AM2011-768