GBM Treatment Research: Immunotherapy Still Prevails

Glioblastomas (GBM), tumors originating from glial cells, are very common primary intracranial malignancies that can cause great harm to the human body. GBM accounts for 27% of all primary central nervous system (CNS) tumors and 80% of CNS malignancies. 5-8 people per 100,000 suffer from it each year, and it lists the 3rd in cancers of the highest 5-year mortality rate only after pancreatic cancer and lung cancer.

However, there is still a lack of precision targeted therapeutic agents for the treatment of GBM, and only 2 drugs, temozolomide (TMZ) and bevacizumab (BV), have received marketing approval from the FDA for the systemic treatment of GBM, leaving a great unmet clinical need. Immunotherapies such as tumor vaccines, CAR-T cells, and oncolytic viruses are expected to fill the gap of precision treatment in the field of GBM treatment.

Tumor Vaccines

GBM-related vaccines are peptide vaccines and dendritic cell (DC) vaccines. Peptide vaccines usually include TSA (tumor-specific antigen) or TAA (tumor-associated antigen) in their structural design. Peptide vaccines developed against brain cancer include single-target vaccines, multi-target combination drugs and individualized vaccines. The DC vaccine functions by being administered back to patients after in vitro modification and amplification of DC cells, thus to enhancing the immune system's ability to recognize and kill tumor cells. However, even after more than 10 years of DC vaccines in GBM and after more than a thousand of patients have been vaccinated, it is still difficult to reach the conclusion to improve the efficacy of DC vaccines.

CAR-T Cell Therapy

CAR-T (chimeric antigen receptor T-cell), is a type of immune cell therapy that kills tumors through the body's own immune cells. T cells are first isolated from PBMC (peripheral blood mononuclear cells) of cancer patients; the T cells are then genetically engineered in the laboratory, and after that, the modified CAR-T cells are infused back.

The main clinical research targets of CAR-T cell therapy for GBM are HER2, IL-13R?2, EGFRvIII, etc. Clinical studies are underway for each of these targets. The challenges of this strategy are how to effectively cross the blood-brain barrier, how to overcome the immunosuppression in the microenvironment of solid tumors, and the serious side effects such as cytokine storm.

Oncolytic Virus Therapy

GBM has very limited therapeutic options because of its insensitivity to radiotherapy in clinical, coupled with the difficulty of the blood-brain barrier. Therefore oncolytic viruses for brain tumor are a potential therapeutic method. Oncolytic viruses are a class of viruses, natural or genetically modified, which can specifically infect and kill tumor cells without causing excessive harmful effects on normal cells.

The future development of oncolytic viruses for brain tumors is mainly in combination with other therapies, such as immune checkpoint inhibitors such as PD-1/L1. In addition, genetic modification of them to carry a more potent combination of immunotherapeutic genes is expected to enhance the single-drug efficacy of oncolytic viruses.

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