PRECISION IMMUNE-ENGINEERING OF THE TUMOR MICROENVIRONMENT

Immunotherapy holds the potential to dramatically improve the
curative prognosis of cancer patients. However, despite significant
progress, a huge gap remains to be bridged to gain broad success in
the clinic. A first limiting factor in cancer immunotherapy is the low
response rate in a large fraction of the patients. The second limiting
factor is immune-related toxicity that can cause live-threatening
situations as well as seriously impair the quality of life of patients.
Therefore, an unmet need exists for more efficient - potentially
synergistic - immunotherapies that improve upon or complement
existing strategies. In this context, the overarching goal of this project
is twofold. On the one hand we will investigate how to turn a cold
tumor with low immune cell infiltration into a hot tumor by local
activation of type I interferon responses in the tumor
microenvironment. Hereto we will design amphiphilic structures that
can restrict the activity of highly potent immuno-modulators (i.e. a
novel class of STING agonists) to the tumor microenvironment and
the sentinel lymph nodes. On the other hand, we will investigate how
to generate synergism with immune checkpoint inhibition, because
upon arrival in the tumor microenvironment, T cells will face an
immune-suppressive halo surrounding the tumor cells. Hereto, we
will investigate nanobody-based checkpoint inhibition and designing
a strategy for a safer, tumor-targeted checkpoint inhibition.