Synthetic cells as immunotherapeutics to remodel the tumour microenviroment

Diseases generate microenvironments with differing physical, chemical, and biological properties compared to healthy tissues. In cancer, the tumour microenvironment (TME) promotes progression and therapy resistance of the most advanced therapeutics including ‘smart’ nanomedicines and engineered cell-based therapies.

While nanomedicines are limited in tunability of function, cell-based therapies can be engineered to modify their microenvironments (e.g. “armoured CAR-T” releasing immune system modulators/cytokines). But they require patient-specific (autologous) manufacturing at very high cost to overcome recognition/destruction by the immune system. In contrast, synthetic cells (SynCells) are non-living molecular compartments engineered to replicate specific biological functions, e.g. the ability to sense their environment and release a distinct drug.

Here, through multi-disciplinary approaches we will demonstrate proof-of-principle that SynCells can be engineered with protein networks sensing and transducing chemical TME signals to release protein drugs (e.g. cytokines, immune checkpoint inhibitors) capable of reactivating the endogenous immune system and clearing the tumour.