Radiation kills cancer cells, but it also takes healthy cells with them. The problem puts radiation oncologists in a bind – higher doses could cure more patients but the collateral damage would put them at greater risk. Paris-based Nanobiotix may have a solution. The company is developing a technology called NanoXray: hafnium oxide nanoparticles (NBTXR3) that have the potential to magnify radiation doses without increasing damage to surrounding tissue.
“With radiation, you always have to cross healthy tissue, so you are limited in the dose you can deliver to the tumor,” said CEO Laurent Levy in a phone interview. “When the patient is getting their usual radiotherapy, these particles absorb nine-fold the energy that the cell can usually absorb, increasing cellular damage.”
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The 50-nanometer particles (50 billionths of a meter) are injected directly into tumors and absorbed by cancer cells. From there, they multiply the radiation’s ability to liberate electrons from water molecules, generate free radicals and hopefully kill cancer cells.
Using physics to fight cancer appealed to Levy and colleagues because it’s indication agnostic. By magnifying the energy directed at cancer cells – without increasing the initial dose entering the body – NBTXR3 nanoparticles could maximize radiation against many cancers.
“In pharma and biotech, you look at cancer and try to find a biomarker – individualized medicine,” said Levy. “We decided to go the other way. These modifications can be used across different cancer types, regardless of the biology.”
Early phase trial results in head and neck cancers have been encouraging. A study released at the recent American Society of Clinical Oncology (ASCO) meeting showed the treatment performed well in older patients with stage III and IV cancers. The nanoparticles were well-tolerated and patient results improved as nanoparticle doses were increased. Seven of the nine patients who received higher doses had complete responses.
“In such a patient, having a complete response means you can go home again,” said Levy. “You can start to eat again, to talk, to swallow.”
Nanobiotix has started a number of trials in liver, head, and neck, rectal and other cancers. The company is also working towards larger trials to validate the early-stage results.
Still, the ceiling for NanoXray may be even higher. The company has been energized by another recent study, which showed NBTXR3 may also support immunotherapy. The phase 2/3 trial studied patients with soft tissue sarcomas and found that adding nanoparticles to radiation increased the levels of immune cells infiltrating tumors, as well as boosting PD1, PDL1, CTLA4 and other immune system genes. Levy believes NanoXray could make tumors more responsive to immunotherapy.
“In immuno-oncology, everyone is trying to transform cold tumors into hot tumors, trying to take patients who don’t respond and try to make them respond,” said Levy. “When you look at the genes that have been upregulated, they are all genes that pharma is trying to target.”
Photo: Ilexx, Getty Images
