High intensity focused ultrasound and mRNA nanomedicines: a new strategy to induce and boost anti-tumor immunity

Cell-based immunotherapies hold great promise for the future
treatment of cancer. Among the recent discoveries in cancer
immunotherapy is the concept of immunogenic cell death (ICD).
When tumor cell death is induced in an immunogenic way, dying
tumor cells can be recognized and engulfed by dendritic cells (DCs),
resulting in DC-activation and tumor antigen presentation. As such,
dying tumor cells can become a cell-based vaccine. This project aims
to investigate HIFU-induced cell death modalities to further maximize
the ICD-inducing potential of high-intensity focused ultrasound
(HIFU), a non-invasive and clinically relevant tumor ablation strategy
that uses ultrasound waves to locally destroy tumor tissue. Following
preliminary experiments, showing HIFU-induced ICD, we want to
further tweak the HIFU-parameters to obtain an optimized protocol
for immunogenic tumor treatment. In synergy with this, we aim to
boost the induced immune responses by the local delivery of immune
checkpoint inhibiting nanobodies by making use of clinically relevant
mRNA nanomedicines that passively target inflammatory monocytes
after systemic injection, which results in high mRNA expression rates
at inflamed areas. As these immune cells are the major source of
immune suppressive cell types in the tumor, they are ideal targets for
tumor modulation, more specific for tackling adaptive resistance
mechanisms.