uTREAT therapy hits aggressive brain tumors while sparing healthy tissue
Early data show treatment was delivered with fewer toxic side effects
Written by |
Preliminary Phase 1 trial data show that uTREAT, Curasight’s experimental targeted cancer therapy, was safely delivered to aggressive solid brain tumors and reached estimated therapeutic levels without exceeding safety limits in healthy organs.
According to the company, these initial findings support the continued development of uTREAT as a potential new treatment option for glioblastoma, an aggressive form of glioma.
“With these data, we are confident in moving forward with the Phase 1 trial and the development program for uTREAT, with the ambition of developing a potentially game-changing radioligand therapy for patients with glioblastoma,” Ulrich Krasilnikoff, CEO of Curasight, said in a company press release.
The challenge of treating glioblastomas
Gliomas are brain cancers that arise from the uncontrolled growth of glia, brain cells that support nerve function. Glioma treatments, including radiation, surgery, and chemotherapy, are often unable to control aggressive forms, and most people with glioblastoma survive little more than a year after diagnosis.
One of the major concerns of current cancer treatments, like radiation and chemotherapy, is that they can also damage healthy cells, leading to significant side effects. As a result, the amount of treatment that can be safely given is often limited, potentially reducing its ability to fully control aggressive tumors.
uTREAT is designed to overcome this challenge. The treatment belongs to a class of medications called radioligand therapies, which use a radioactive molecule attached to a delivery vehicle to seek out and destroy cancer cells. Specifically, the therapy targets the urokinase-type plasminogen activator receptor (uPAR), a protein expressed at high levels on cancer cells but generally absent in healthy adult tissues.
By attaching a radioactive molecule to a small protein fragment that binds to uPAR, uTREAT aims to deliver cancer-killing radiation directly to uPAR-expressing tumor cells while minimizing exposure to surrounding healthy tissue.
Unlike antibodies used to carry radioactive molecules in some other radioligand therapies, the peptide used in uTREAT is rapidly cleared from the bloodstream. This means that any therapy that does not bind to its target is quickly eliminated from the body, potentially reducing radiation exposure to healthy organs.
The therapy is administered through a catheter placed directly into the blood vessels that feed the tumor using a technique called super-selective intra-arterial cerebral injection, or super-SIACI. Before the therapy is delivered, the blood-brain barrier — a protective layer that normally limits the passage of substances from the bloodstream into the brain — is temporarily opened with mannitol, a sugar-based compound. This approach is designed to help more of the therapy reach the tumor while limiting radiation exposure to healthy tissues.
The ongoing Phase 1 trial is evaluating the safety, distribution, and radiation dosing of uTREAT in people with newly diagnosed, confirmed, or suspected glioblastoma.
Earlier this year, Curasight reported that PET scans (using the company’s uTRACE system) from the first glioblastoma patient treated in the study showed high and sustained uptake of uTREAT within the tumor, providing initial evidence that the therapy could selectively and strongly bind to glioblastoma cells — a key requirement for delivering cancer-killing radiation directly to the tumor.
The newly announced preliminary readout showed that delivery of uTREAT using the super-SIACI approach was feasible and safe. Researchers also observed high uptake and retention of uTREAT within tumors.
Analyses of biodistribution, or how the therapy spreads through the body, and dosimetry, which estimates the radiation dose delivered to tissues, suggested uTREAT could deliver therapeutically relevant radiation doses to tumors without exceeding safety limits for healthy organs.
“The preliminary readout of our Phase 1 clinical trial with uTREAT in glioblastoma is encouraging and supports the ability of our technology to safely deliver therapeutically relevant radiation doses to the tumor without reaching dose limits for healthy organs,” Krasilnikoff said.
