Hafnium oxide nanoparticles with radiotherapy induce immunogenic cell death

Summary

Background: Between 70 to 90% of patient have « cold » tumors, i.e. devoid or poorly infiltrated by immune cells, rendering inoperative their treatment by immune checkpoint inhibitors. To allow these patients to benefit from these therapies, it is fundamental to prime an antitumor immune response. Radiotherapy (RT) has demonstrated its ability to induce the immunogenic cell death (ICD), a crucial event allowing the priming of the antitumor immune response. Meanwhile, a new class of material with high electron density, hafnium oxide, was designed at the nanoscale (HfO2-NP) to efficiently absorb ionizing radiation and increase the radiation dose deposition from within the tumor cells and increase killing of cancer cells. Here, we compared the ability of HfO2-NP and RT to RT alone to kill cancer cells and induce immunogenic cell death.

Methods: A panel of human and mouse cancer cell lines (mesenchymal and epithelial origin, radiosensitive and radioresistant) were treated or not with HfO2-NP, then irradiated by X-rays. Impact of the treatments on apoptosis and necrosis was assessed by FACS analysis (Annexin V/Propidium iodide). […]

Results: For all the tested cell lines treated with HfO2-NP and RT, a marked increase of apoptosis and necrosis was demonstrated, compared to cells treated with RT alone. In addition, higher levels of DAMPs (ecto-CRT, ecto-HSP70, ecto-HSP90, secreted ATP and extracellular HMGB1) were measured in the cancer cells treated with HfO2-NP and RT when compared to cancer cells exposed to RT.

Conclusions: HfO2-NP has demonstrated its capacity to kill cancer cells more efficiently than radiotherapy alone. HfO2-NP, administered via a single intratumor injection, is currently evaluated in clinical trials including soft tissue sarcoma (phase II/III), head and neck, prostate, liver and rectum cancers (phase I) and would permit to improve the local control of tumors, a crucial parameter for the cure and survival of patients. […]