Some blood cancer treatments have been revolutionized thanks to CAR-T therapies that modify patients' T cells to target proteins linked to cancer.
So far, though, these treatments have not successfully managed to show much potential against solid tumors such as the aggressive brain cancer glioblastoma.
Now, a team of researchers from City of Hope has created a new chimeric antigen receptor (CAR) based on chlorotoxin (CLTX) — a toxin found in the venom of scorpions.
Their findings were published in Science Translational Medicine.
Challenges in targeting tumors
Targeting glioblastoma (GBM) is tricky due to the diversity of the tumors. In order for CAR-T to work, the CARs on the T cells' surface have to be able to latch onto tumors that have different genetic variations.
In their research, the scientists set out to discover a better CAR guide to target T cells with strong GBM binding activities. The binding ability is useful in controlling the invasive nature of tumors.
"We are not actually injecting a toxin but exploiting CLTX's binding properties in the design of the CAR," study author Michael Barish, who initiated the CLTX CAR development for GBM, said in a statement. "The idea was to develop a CAR that would target T cells to a wider variety of GBM tumor cells than the other antibody-based CARs."
The team tested their novel CAR-T treatments on mouse models with patient-derived tumors. What they discovered was that the treatment controlled tumor growth and prolonged the life of the mice.
"Much like a scorpion uses toxin components of its venom to target and kill its prey, we’re using chlorotoxin to direct the T cells to target the tumor cells with the added advantage that the CLTX-CAR T cells are mobile and actively surveilling the brain looking for appropriate targets," Barish said.
He continued, "We are not actually injecting a toxin, but exploiting CLTX’s binding properties in the design of the CAR. The idea was to develop a CAR that would target T cells to a wider variety of GBM tumor cells than the other antibody-based CARs."
From Scorpion to Immunotherapy City of Hope Scientists Repurpose Natures Toxin for FirstofIts Kind CAR T Cell Therapy to Treat Brain Tumors: The research published today and scorpion venom will also be key component of CAR T cell therapy for glioblastoma… https://t.co/d7GgBJ6fa8— Cancer News (@Cancer_bio) March 4, 2020
The engineered T cells only stuck to the tumor cells, leaving the brain tissue around them intact. Moreover, the treatment did not cause any adverse side effects or organ damage to the animals.
The team has already received approval from the Food and Drug Administration to proceed, and they are screening potential patients for their first human clinical trial.