The majority of anticancer immunotherapies focus on blocking the inhibitory immune-checkpoint receptors and reactivating the existing primed T cells. However, these therapeutic strategies rely on a previously initiated cancer-immunity cycle. Such prior initiation may not be globally applicable to all tumours. In fact, the response rate of treatments like anti-PD1 or anti-CTLA4 is limited to 20-30%. Hence, therapies that initiate the cancer-immunity cycle by increasing the immunogenic signals for the innate immune system need prioritization.

This could be achieved by blocking the “phagocytosis-checkpoints” like ´don’t eat me’ signals, hence increasing cancer antigen uptake and presentation by innate immune cells. However, this subgroup of antibodies (Abs) has severe limitations, including adverse effects and a low efficiency. In fact, murine tumour models treated with Ab-based phagocytosis-checkpoint blockers displayed a short window of therapeutic efficacy followed by a relapse.

Hence, there is a clear unmet need for innovative Ab-based strategies that allow prolonged local Ab exposure in the tumour combined with efficient intra-tumoral delivery. Additionally, we found that combining such Abs with other specific biologics (e.g., intra-tumourally-delivered cytokines) can massively increase the anticancer efficiency.

 For this, Ab-gene transfer integrating multiple biologics presents a highly innovative solution. The principle of this approach is to administer the plasmid DNA (pDNA) that encodes the Ab (and other biologics) to the tumour, resulting in combined production of the therapeutic Ab/biologics for a prolonged period. Nanomedicine is a major mediator for the local delivery of pDNA to protect the encapsulated cargo and prevent premature degradation, or off-target activity. In this project, we aim to design Ab/biologics-encoding pDNA-nanoformulations to drive local and prolonged therapy exposure in the tumour to exploit phagocytosis-driven anticancer immunity.