Pur-Ther

Immunotherapy is based on the concept that we should re-activate the physiological anti-tumor immune response rather than kill tumour cells with chemotherapy. This efficient therapeutical strategy is based on the blockade of molecules called Immune checkpoints and has revolutionized current oncological treatments. However, immunotherapy has drawbacks since it often activates immune-mediated aggression of healthy tissues or tumors become refractory. Therefore, novel pathways modulating the anti-tumor immune response without side effects needs to be identified. Tumors are rich in ATP, a molecule playing several roles, including stimulation of immune cells, promotion of tumor proliferation, and generation of an immunosuppressant named adenosine. We have developed original techniques to measure ATP in tumors and verify how its concentration changes in response to therapy. We also developed highly innovative small antibodies named nanobodies raised against molecules interacting with ATP inside tumors called “purinergic checkpoints”. We plan to verify whether this weaponry of highly innovative reagents will improve the therapy of three tumors selected for their resistance to immunotherapy: lung adenocarcinoma, glioblastoma multiforme, and multiple myeloma. We will test the effect on the growth of experimental tumors of nanobodies highly selective for the purinergic checkpoints. In addition, we will explore the impact of the combined administration of purinergic checkpoints and immune checkpoints. Finally, with this project, we plan to set the basis for first-in-man experimentation to verify the efficacy of the combined administration of immune checkpoint blockers together with selected purinergic checkpoint inhibitors.
We are confident that our efforts will pave the way to the definition of novel and effective anti-cancer therapeutic protocols.