IL-13 can substitute for IL-4 in the generation of dendritic cells for theinduction of cytotoxic T lymphocytes and gene therapy

Immunization with tumor-associated antigen pulsed dendritic cells (DC) has been shown to elicit both protective and therapeutic antitumor immunity in a variety of animal models and is currently being investigated for the trea tment of cancer patients in clinical trials. In this study we show that DC can be generated from peripheral blood mononuclear cells of healthy donors as well as breast and melanoma cancer patients using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-13 (IL-13) and that the se DC have many of the same characteristics as DC differentiated using GM-C SF and IL-4. The DC generated in GM-CSF and IL-13 are CD14(-) and express h igh levels of the cell surface markers CD86, HLA-DR, and CD58, as do DC gen erated in GM-CSF and IL-4. The purity and yield of both DC populations are not significantly different. Furthermore, both populations of DC are effect ive at presentation of alloantigen as determined in a mixed lymphocyte resp onse, and both are able to process and present soluble tetanus toroid antig en to CD4(+) T cells, Because we are interested in the generation of DC for antigen-specific cytotoxic T lymphocyte (CTL) generation, we compared the ability of peptide-pulsed DC differentiated in GM-CSF and IL-4 versus GM-CS F and IL-13 for the generation of influenza and MART-1 specific CTL. Both p opulations of DC induced CD3(+)CD8(+)CD4(-) and CD56(-) CTL, which could ly se the appropriate targets in an antigen-specific manner. Finally, both CM- CSF and IL-4 DC and GM-CSF and IL-13 DC yielded similar beta galactosidase expression levels after transduction with recombinant adenovirus containing the LacZ gene. These results suggest that DC generated in GM-CSF and IL-13 may be useful for immunotherapy and gene therapy protocols.