Cytokine gene transfer into dendritic cells for cancer treatment
Tirapu I, Rodriguez-Calvillo M, Qian C, Duarte M, Smerdou C, Palencia B, Mazzolini G, Prieto J, Melero I.
Gene Therapy Unit, Dept. of Medicine, University of Navarra, Pamplona, Spain.
Bone marrow-derived dendritic cells have been used to treat established experimental tumors by unleashing a cellular immune response against tumor antigens. Such antigens are artificially loaded onto dendritic cells' antigen-presenting molecules by different techniques including incubation with synthetic antigenic determinants, tumor lysates or nucleic acids encoding for those relevant antigens. Ex vivo gene transfer with viral and non-viral vectors is frequently used to obtain expression of the tumor antigens and thereby to formulate the therapeutic vaccines.
Efficacy of the approaches is greatly enhanced if dendritic cells are transfected with a number of genes which encode immunostimulating factors. In some cases, such as with IL-12, IL-7 and CD40L genes, injection inside experimental malignancies of thus transfected dendritic cells induces complete tumor regression in several models. In this case tumor antigens are captured by dendritic cells by still unclear mechanisms and transported to lymphoid organs where productive antigen presentation to T-cells takes place. Many clinical trials testing dendritic cell-based vaccines against cancer are in progress and partial clinical efficacy has been already proved.
Transfection of genes further strengthening the immunogenicity of such strategies will join the clinical club soon.
CITATION Curr Gene Ther. 2002 Feb;2(1):79-89