Nano-vehicles as a Platform for Tracking and Immunochemotherapy of Cancer

Vidi Grant

Cancer therapy can be made more efficient by combining targeted chemotherapy delivery with immunotherapy. Nano-vehicles, such as liposomes or polymeric nanoparticles, can be used to visualize cancer cells, protect and deliver chemotherapy, and simultaneously modulate the immune system, either systemic or in situ.

One of the aims in this project is to reduce the side effects of chemotherapy by utilizing nanoparticles. One method we can employ to achieve this, is to reduce the chemotherapy dose. To make sure that the capacity of killing cancer cells is not lost, we assemble nanoparticles to deliver a low-dose of chemotherapy directly to cancer cells. By actively targeting cancer cells using specific cancer cell receptor ligands, there is less chemotherapy required which leaves most healthy cells left unaffected. As such, side effects of chemotherapy are considerably reduced whilst maintaining the effective capacity to kill cancer cells. In addition, to augment the killing capacity of chemotherapy, we are studying the most potent chemotherapy combinations as well as their capacity to induce immunogenic cancer cell death.

On the other hand, some cancer cells may develop mechanisms of resistance against chemotherapy, change their molecular make-up and metastasize to regions of the body that are difficult to reach for nanoparticles. To anticipate this response, we aim to modulate the immune system to recognize cancer cells and at the same time provide the right cues necessary to licence immune cells to kill the remaining or metastasized cancer cells. This is a very promising strategy, as immune cells can locate cancer cells at sites in the body that nanoparticles cannot reach. Additional acquired traits include immunological memory, which ensures prolonged fighting against cancer cells, and rapid reactivation of the immune system in the event any cancer cell escaped detection and resurface years later. For this purpose, we employ member ligands of the Toll-Like receptors and other powerful immune stimulants that we co-encapsulate in our nanoparticles together or separately with chemotherapy. These nanoparticles are then targeted to the tumor microenvironment or to specific subset populations of the immune system. We also study the combination of these nanoparticles combined with immune check-point blockers, cancer vaccines, or small inhibitor molecules.