A study by investigators at the Dana-Farber Cancer Institute suggests that neoantigens could play a role in treating glioblastomas. Patients in this study received a personalized vaccine that led to longer survival compared to most patients with glioblastomas, suggesting that selectively stimulating these tumors could be the key to curing them.
Glioblastomas are malignant brain tumors that are usually slow growing but can become aggressive. By the time these tumors are discovered, they are typically Grade IV, meaning they grow rapidly, have bizarre cellular appearances and easily infiltrate nearby brain tissue. They are also capable of forming new blood vessels (angiogenesis), which allows them to absorb more nutrients and continue growing. In addition to their location and rapid growth, glioblastomas are “cold” tumors, meaning they contain very few immune cells. Immune cells are recognized by the body as cells requiring action; since these tumors contain very few of those cells, the immune system does not respond properly.
To combat the lack of immune cells, David Reardon, clinical director of the Center for Neuro-Oncology at Dana-Farber, performed a study with a neoantigen vaccine for glioblastomas, published in Nature. The vaccine used in the study was a personalized ‘neoantigen’ serum that caused an immune response against glioblastomas. Like other cancers, glioblastomas contain DNA mutations that cause cells to reproduce rapidly and create tumors. Some of these mutations, including those in glioblastomas, cause cancer cells to display peptide molecules — or neoantigens — on the cell’s surface. Neoantigens are not present on healthy cells, making them relatively easy targets for the immune system.
To attack the tumor cells, researchers created personalized vaccines by removing and analyzing tissue from tumor and healthy cells in the patient. Once they identified which neoantigens were present in the tumor, proteins from the neoantigens were synthesized in a laboratory to form the base of the vaccine. After being administered, the vaccine encourages the body to create T-cells that migrate to the brain tumor, causing inflammation around the cancer cells. Then, the neoantigens in the serum “teach” the patient’s immune system how to detect and attack tumor cells.
The eight patients in the study received vaccines containing between seven and twenty neoantigen peptides. All of the patients ultimately died from their tumors, but they survived longer than average for glioblastoma patients. Reardon is encouraged by the results of this preliminary study.
“The next step is to add an immunotherapy drug called a checkpoint inhibitor, aimed at freeing the immune response from molecular ‘brakes’ so that the T-cells can react more strongly against the tumor,” Reardon said.
The combination of a neoantigen vaccine with a checkpoint inhibitor should lead to a stronger immune response and potentially extended survival without tumor spread and thus, the possibility of a cure.