Researchers Experiment With Boosting Dendritic Cell-Based Immunotherapy Against Glioblastoma

Researchers Experiment With Boosting Dendritic Cell-Based Immunotherapy Against Glioblastoma

shutterstock_118491940In a recent study entitled “Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients,” researchers showed that boosting the immune system with a tetanus vaccine before administering a dendritic cell vaccine enhances glioblastoma multiforme patients’ immune response, leading to increased survival. The study was published in the journal Nature.

Dendritic cells are antigen-presenting cells and are responsible for processing antigens (any foreign substance, such as chemicals, bacteria, viruses that induce the immune system to produce antibodies against it) and presenting it on their cell surface to T cells. They have been used in cancer immunotherapies to target several different kinds of tumors. The process relies on extracting dendritic cells from patients’ blood, followed by reengineering dendritic cells to express antigens from the tumor. When injected back into patients, the dendritic cells then work as a vaccine — they migrate to lymph nodes and by expressing tumor antigens at their surface induce T cells’ activation against the tumor.

In this study, a research team from Duke University Medical Center sought to understand whether enhancing dendritic cell migration towards the lymph nodes would increase dendritic cell-based vaccines for the most aggressive form of brain cancer in adults, glioblastoma multiforme.

The authors pre-conditioned the dendritic cell vaccine with an antigen from cytomegalovirus. The vaccine was administered into newly diagnosed glioblastoma patients who were distributed into two groups — one received the vaccine alone (control group), while the other was administered a tetanus vaccine, to work as a booster and activate the immune system prior to the cytomegaloviral antigen equipped vaccine.

The team showed that enhancing the immune system with a tetanus vaccine before administering the dendritic cells led to their increased migration into lymph nodes, increasing patients’ survival to 3 years after diagnosis (in the control group the survival was 1.5 years).

The reason behind these different outcomes seems to rely on specific memory T cells that the tetanus booster vaccine generated, crucial for later dendritic cell migration into lymph nodes. Additionally, two chemokines, CCL3 and CCL21, were also important in this migratory process.

The team now wants to perform larger clinical trials to validate the use of boosting strategies and targeting cytomegalovirus as a possible future therapeutic against glioblastomas.

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