Immunotherapy Frontiers for Brain Tumors

Immunotherapy Frontiers for Brain Tumors

October 31, 2019

Scientists have made strides in treating many forms of cancer in recent years, using a technique known as immunotherapy. In these treatments, the patient’s own immune system gets recruited to help fight tumors. Yet to date, brain tumors have remained hard to treat with immunotherapy. Now some new approaches to immunotherapy, including CAR T cell treatment, may offer new hope.

We all have cancer cells in our body. This is an inescapable fact our biology works. Yet most of the time, these cancer cells don’t grow into tumors. That is because a part of our immune system called T cells are constantly circulating the body, locating dangerous lines of cancer cells and destroying them. So tumors must evade the immune system to grow, but once underway, they have ways of shutting the immune system down.

This is true in brain tumors as well. GBM patients often show signs of lowered immune system activity. T-cells seem to be missing in action in many GBM patients.

The key step in immunotherapy treatments is to remove the brakes that a tumor puts on the immune system. Drugs like nivolumab or pembrolizumab are commonly used for this purpose. Yet by themselves, these haven’t proven very effective for most glioblastoma tumors.

The blood-brain barrier is one factor. Another, suggested by researchers at Columbia University, may be due to how tightly cancer cells are packed together in a brain tumor, making it hard for immune system agents to penetrate. Dr. Mark Gilbert of the NIH added that the steroids, which many brain tumor patients must take to control swelling, may further blunt immune response.

CAR T cell treatments are a promising technique that extend normal immunotherapy and supercharge it. First, some of a patients T cells are removed from the body. Then their DNA is modified to make them much more aggressively target a protein called a chimeric antigen receptor (CAR), which is found on the surface of many tumors. The newly modified cells are then grown in the lab to counts in the hundreds of millions, and then injected back into the patient to go to work.

CAR T cell treatments use an targeted, supercharged version of the patient’s own immune system to attack tumors.

The Brain Tumor Center at University Hospital Zurich tested a CAR T cell treatment in which the cells were programmed to attack a specific protein that is overexpressed in glioblatoma, and infused into the tumor cavity. They observed regression tumor tissue when the treatment was completed. Furthermore, the investigator in that study, Michael Weller, reported that they did not see significant toxicity in patients on the treatment.

Separately from the CAR T investigations, researchers at Duke Cancer Center have observed cases where the body’s normal store of T cells, which should circulate the body, are being signaled by the GBM tumor to “stay home,” remaining trapped in bone marrow where they are created. The Duke team is working with other scientists to find ways to reverse the process that deactivates T-cells, opening up promising new options for glioblastoma treatment.