Priming with Dendritic Cells Can Generate Strong Cytotoxic T Cell Responses to Chronic Myelogenous Leukemia Cells In Vitro

Abstract

Dendritic cells (DC) are antigen-presenting cells that can elicit potent antigen-specific responses. Since the development of techniques to cultivate these cells from peripheral blood, there has been a great deal of interest in their use in immunotherapeutic strategies. Here we show that morphologically, phenotypically, and functionally characteristic DC can be generated in vitro from peripheral blood mononuclear cells (PBMC) isolated from frozen apheresis product (AP) of cancer patients. These DC, when pulsed with whole-tumor lysate, protein, or RNA from a chronic myelogenous leukemia (CML) cell line, can induce anti-CML specific cytotoxicity in vitro by autologous cytotoxic T lymphocytes (CTL). RNA and protein-pulsed DC were more effective than lysate-pulsed DC at inducing cytotoxicity at low effector:target(E:T) ratios. These results were comparable to those obtained when fresh healthy peripheral blood was used as the source of PBMC, indicating that neither the malignant state of the patient nor the storage period detrimentally affected the generation or functionality of DC. CML cells were found to increase their level of MHC class I expression after exposure to CTL and pulsed DC thereby becoming better targets. These investigations lend support for the utilization of DC to generate anti-tumor responses in CML.