In vitro sensitization of T lymphocytes for analysis of the immunostimulation ability of dendritic-tumor cell hybrids

Abstract

Dendritic cells (DCs) are professional antigen presenting cells highly used in immunotherapy protocols since their generation in vitro from monocytes was described. To induce antitumor responses, DCs need to be loaded with tumor antigens. Due to the tumor heterogeneity, it is preferable to load DCs with a pool of antigens, a process that can be reached by using tumor cell products. One way to generate a tumor polyantigenic response is to use the fusion of dendritic and tumor cells. These hybrids were described as able to induce robust immune responses, but not so satisfactory clinical responses in most cases. These relative failures may be a consequence of the defects encountered in the dendritic cells generated from monocytes obtained from cancer patients. Thus, one can use, to generate the hybrids, DCs differentiated from monocytes of healthy unrelated donor. Besides presenting tumor antigens with the necessary costimulation, these semi-allogeneic hybrids may also subvert the tumor-favoring equilibrium with the immune system by inducing a potent allogeneic effect. However, it is not well known if these hybrids can induce an antigen specific response against the tumor. Thus, the aim of this work is to evaluate the ability of these semi-alogeneic hybrids to induce antigen specific CD8+ T cells in comparison with the well established response induced by Smart-DCs. To do so, we will use cells from high-risk acute myeloid leukemia (AML) patients that have been collected during active disease and after remission, as a source of tumor cells and or autologous effector T cells, respectively. Tumor cells will be used to generate the DC-tumor hybrids and these will be used as stimulators of patients´ T cells. (AU)