Research
DanDrit’s research and development activity is focused on improving the methods of dendritic cell vaccination. Previous work has led to the development and patent filing of an improved and unique method for culturing, expansion and maturing of dendritic cells obtained from peripheral blood monocytes. This new method is currently in the process of patent filing world-wide and is used in the production of MelCancerVac®.
Our research and development projects involve both the improvement of existing technologies and the discovery of new methods for using dendritic cells to treat disease.
Tolerogenic Dendritic Cells
In MelCancerVac® dendritic cells are derived in such a way that the resulting dendritic cells are immunogenic, they promote an immune reaction. However, dendritic cells may also be derived in such a way that they are tolerogenic, they promote immune tolerance. Promoting immune tolerance can be used to treat autoimmune diseases such as type I diabetes or even to help prevent rejection of tissue transplantation. In this way the tolerogenic dendritic cells are used to turn off an undesirable immune reaction.
We have established methods to derive tolerogenic dendritic cells from peripheral blood monocytes, similar to the approach used to generate immunogenic dendritic cells in MelCancerVac®. Tolerogenic dendritic cells are easily distinguished by their function in vitro. We are currently in the process of filing a patent to cover the generation of tolerogenic dendritic cells and are looking for a partner to initiate clinical trials using this system.
Fast Track Generation of Dendritic Cells
The generation of mature immunogenic dendritic cells from peripheral blood monocytes requires 8 days of growth in culture. The efficiency of producing MelCancerVac® will be greatly improved if the time required to generate dendritic cells could be significantly reduced. We have tested many protocols for generating dendritic cells quickly, from these trials has emerged 2 promising methods to generate dendritic cells in either 2 days or 5 days. The fast track methods for generating dendritic cells produce immunogenic dendritic cells that are comparable to cells generated using DanDrit’s standard technique. These new fast track methods are covered by our existing dendritic cell technology patent and we expect to publish the results in a peer-reviewed journal article.
Identification of Tumor Antigen Expression by Quantitative PCR
DanDrit’s therapeutic cancer vaccine, MelCancerVac®, is based on loading patient dendritc cells with a specifically selected allogeneic tumor cell lysate. In order to better define the tumor antigens expressed in DanDrit’s tumor lysate we have developed real-time PCR assays for more than 60 different tumor antigen genes or gene families, including 35 genes with confirmed T cell peptide epitopes. In addition to testing for the presence of molecular expression in DanDrit’s cell lysate we have begun screening patient tumor biopsies for the expression of tumor antigens. The real-time PCR assay we have developed is capable of assaying up to 37 different tumor antigen genes (+ 3 control genes) in a single run on a 96 well plate. Gene expression is determined as a ratio to GAPDH expression and is then compared to patient matched normal tissue in order to detect tumor-specific changes in gene expression. We are planning to develop this assay as a commercially available tumor antigen PCR kit supplied as an array of tumor antigen specific PCR primers dried in a 96 well PCR plate.