Numerous strategies to elicit tumour specific immune responses are under investigation, amongst which the use of lentiviral vectors (LVs) for in situ delivery of tumour-associated antigens to antigen presenting cells, such as dendritic cells (DCs).
In this project we aspire to improve LV-based anti-tumour vaccines. To that end, we will address several key issues, such as (i) the role of cross-presentation and direct transduction of DCs in the induction of transgene responses upon LV vaccination, (ii) which DC subtype is best suited to induce effective anti-tumour immunity and (iii) how to improve the immune stimulatory capacity of these DCs. Therefore, we will exploit state of the art LV technologies, including (i) microRNA (miRNA) management of transgene expression to de-target expression in hematopoietic cells (miRNA 142-3p) and non-hematopoietic cells (miRNA 126), (ii) DC subtype-specific Nanobodies to target LV entry and (iii) silencing of signalling molecules critical in pathways activated in DCs upon transduction.
The insights that we gain from this project will enable the rational design of LV-based vaccines, not only for the treatment of cancer and infectious diseases, but moreover for the treatment of transplantation rejection and autoimmune diseases.