Phase 2 trial aims to identify which tumors are most likely to respond to treatment

By Alejandra Canales and Ilona Garner
Illustrations by Terry Nguyen

Immunotherapies are a type of cancer treatment that tries to get the body to recognize tumor cells as foreign so that the immune system can mount a response against them.

Immune checkpoint proteins moderate this response so that your immune system doesn’t start attacking normal cells. In the setting of cancer, these checkpoint proteins can be a barrier to effective immunotherapy. 

Immune checkpoint inhibitors are a class of drugs that bind to these proteins and take the brakes off the T cells. This action forces the body to recognize and destroy the tumor cells.

The way that the immune system functions in the brain is different than in other organs. While there are immune cells present, they are fewer and more tightly regulated to prevent them from damaging the brain with an unchecked immune response.

When T cells get activated to fight glioma, other immunosuppressive cells also respond — as an added check on the immune response and can stop the T cells. This immunosuppressive environment is difficult to overcome.

As part of a new phase 2 clinical trial at the UCSF Brain Tumor Center, patients with glioblastoma who are experiencing their first disease recurrence will receive the immune checkpoint inhibitor atezolizumab (1)  before surgery to remove their tumor.

(2) The surgery physically removes immunosuppressive cells that appear after the first dose. This allows the T cells stay on high alert against any tumor cells that remain after surgery or attempt to regrow. (3) Participants then receive a second dose after surgery.

An important part of this study will be trying to understand which patients would benefit most from this immunotherapy.

By studying each tumor’s genetic makeup and testing blood samples, the researchers will create a profile of the genetic and immune factors that would make a tumor more vulnerable to atezolizumab.

Because glioma cells can vary from one area to another within the same tumor, tissue samples will be taken from multiple sites to fully understand its composition. This spatial profiling analysis was developed at UCSF.

For more information:

A Multicenter Trial to Identify Optimal Atezolizumab Biomarkers in the Setting of Recurrent Glioblastoma: The MOAB Trial

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