Further development of mRNA Galsomes as nanovaccines for cancer immunotherapy: combination with checkpoint inhibition and translation to the clinic.

We recently developed Galsomes, nano-sized particles that trigger a broad antitumor immune response after intravenous delivery. Upon infusion, these nanovaccines specifically target immune cells to which they simultaneously deliver genetic material (mRNA) encoding tumor antigens as well as glycolipids. As a result, as they manage to engage multiple immune effector cells, including Natural Killer T (NKT) cells and cytotoxic T cells (CTLs) to attack a growing tumor. This project aims to further explore the full potential of these Galsome vaccines, while paving the way for their clinical translation. As such, we aim to modify the Galsome formulation to enable a rational combination with checkpoint inhibitors, as these clinically approved moieties are expected to strengthen the evoked immune response, enable prime-boost vaccinations, and counteract immune suppression at the tumor site. Secondly, we will investigate and optimize the formulation to enable the inclusion of different types of mRNA-encoded tumor antigens. Since most mutations that can be efficiently recognized by immune cells are tumor- and patient-specific, we aim to incorporate these into the Galsomes to steer the antitumor immune response. Finally, we will perform a rational, step-wise translation of the Galsome-induced immune responses from mouse to man and perform extensive preclinical toxicology studies. This way, we aim encourage the further evaluation of Galsomes in human clinical trials in the near future.