Glioblastoma (GBM) is an aggressive form of cancer that begins in the brain and results in tumors that can be very difficult to treat. This condition has claimed the lives of Beau Biden, former Vice President Joe Biden’s son, and John McCain, former Senator of Arizona. However, a new approach to combat this condition is being developed at City of Hope and has just received approval from the FDA to conduct clinical trials. The innovative approach involves using a combination of chimeric antigen receptor (CAR)-T cell therapy and specific components of scorpion venom!

Before we dive into how the scorpion venom is being used, what exactly is CAR-T cell therapy?

This approach consists of using T cells, which are an immune system cell that can destroy foreign or abnormal cells, and modifying them with a protein called a chimeric antigen receptor (CAR). These newly designed CAR-T cells are able to identify and destroy cancer cells by detecting a specific protein on these cells. What makes CAR-T cell even more promising is that the specific protein detected can be set to virtually anything.

This is where the scorpion venom comes into play. One of the components of this venom is called chlorotoxin (CLTX), which has the ability to specifically bind to brain tumor cells.

For this study, Dr. Christine Brown, Dr. Michael Barish, and a team of researchers at City of Hope designed CAR-T cells using chlorotoxin in order to specifically detect and destory brain tumor cells. Now referred to as CLTX-CAR-T cells, they found that these newly engineered cells were highly effective at selectively killing brain tumor cells in animal models. What’s more remarkable is that the CLTX-CAR-T cells ignored non-tumor cells in the brain and other organs.

In a press release, Dr. Barish describes the CLTX-CAR-T cell approach in more detail.

“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 target. 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.”

In the same press release, Dr. Brown talks about the promise of this newly developed therapy.

“Our chlorotoxin-incorporating CAR expands the populations of solid tumors potentially targeted by CAR T cell therapy, which is particularly needed for patients with cancers that are difficult to treat such as glioblastoma. This is a completely new targeting strategy for CAR T therapy with CARs incorporating a recognition structure different from other CARs.”

The first-in-human clinical trial using the CLTX-CAR T cells is now screening potential patients.

CIRM has funded a separate clinical trial conducted by Dr. Brown that also involves CAR-T cell therapy for brain tumors.

The full results of this study was published in Science Translational Medicine.

A video talking about this approach can also be found here.