Dendritic cells (DC) are key mediators of immunity and targets of therapeutic vaccination strategies. Clinical trials demonstrated the safety and immunogenicity of autologous monocyte-derived DCs loaded ex-vivo with tumour antigens, yet revealed a defect in the migratory pathways of these cells and only a minor fraction of patients exhibited clinical responses. These challenges highlight the need to develop new methods that allow the direct delivery of antigens to DCs in-vivo by injecting antigens fused to a DC targeting moiety. Targeted in-vivo strategies should benefit from reaching multiple DC subsets in their natural environment.
We have bio-panned peptide phage libraries on humans DCs and selected several DC-binders. One of the selected peptides, named NW peptide, bound with high affinity to various DC subsets and human monocytes, precursors of inflammatory DCs. Therefore, this peptide can be used to target antigens of choice to DCs ex-vivo and in-vivo . Coupling of this peptide to multiple peptide- and nucleic acid effector molecules has been shown to result in efficient antigen presentation and generation of CD8+ cytotoxic T-cell responses in vitro, as well inhibit tumour cell growth in vivo. We also believe that the technology is suitable for treatment of autoimmune diseases characterized by abnormal monocyte/macrophage phenotype and function.
We are in the process of expanding our documentation of in vivo targeting in xenograft models of cancer and lupus nephritis.
An international patent application (WO 2014/184683A2) protecting the invention has entered national stage in US and EP, with favourable ISR/WO of patentability.