Researchers Identified Way to Improve Effects of Immunotherapy For Glioblastoma
When cancer attacks, it may be possible for sufferers to fight back with their own defences, making use of an approach known as immunotherapy. With respect to a new research presented in Nature, investigators have identified a way to improve the effects of this therapeutic strategy in glioblastoma, a dangerous kind of brain cancer, and probably enhance patient outcomes. The study was backed by the National Institute of Neurological Disorders and Stroke (NINDS) along with the National Cancer Institute (NCI).
Duane A. Mitchell, co-lead author of the study stated “The promise of dendritic cell-based treatment and other immuno-therapies for brain cancer has been upheld for some time, but an essential implication of this work is a shown capability to significantly enhance the clinical effect of immunotherapy for sufferers with this extremely difficult disease.”
Dendritic cells are specific immune cells that generally capture microorganisms, and then move to the lymph nodes to prepare other immune players, like as T cells, to protect against the invaders.
Dendritic cells have been utilised for immunotherapy to target a wide range of tumor types, such as those that affect the brain. These cells are obtained from the patient, engineered to express antigens from the tumor to develop a vaccine, and then injected back into the sufferer. Once in the patient, the engineered dendritic cells stimulate T cells, which can attack the tumor and also stop it from coming back, via an immune memory response.
Dr. Mitchell and his colleagues desired to know if increasing dendritic cell migration to lymph nodes would enhance the outcomes of the vaccine. To examine this idea, a group of glioblastoma sufferers was randomized to obtain a tetanus booster shot prior to obtaining the tumor-antigen expressing dendritic cell vaccine. The enhancer was developed to set off an inflammatory reaction at the site of the vaccination, preparing the immune system for a bigger battle. The other group of sufferers were injected with their own native dendritic cells instead of a tetanus shot, and then handled with the tumor-antigen expressing dendritic cell vaccine. Both sets of sufferers were treated with the vaccine which was being examined for effectiveness against glioblastoma.
The vaccine used in this research was aimed against cytomegalovirus (CMV). Studies have proven that CMV is identified in glioblastoma tumors, but it is not clear if the virus leads to tumors or contributes to disease advancement. Glioblastomas are a harmful type of brain cancer with 5 year survival time below 10%. From the time of diagnosis, average survival rate is under two years.
Jane Fountain, program director at the NINDS at NINDS stated “The role of CMV in glioblastoma has been a debatable area of research for numerous years. These new results, and particularly the dramatic survival rates, recommend that the virus may be an effective target for immune therapy. The outcomes provided by Dr. Mitchell and his colleagues should encourage more primary research on CMV and its possible therapeutic role in brain tumors and probably other cancers.”
The outcomes revealed that providing a tetanus booster prior to the vaccine enhanced dendritic cell migration to lymph nodes and also had a considerable effect on clinical outcomes. The sufferers who obtained the tetanus booster lived more than 36.6 months following diagnosis in comparison to an average survival rate of 18.5 months in those who obtained dendritic cells only.
Dr. Mitchell stated “We did not assume that boosting dendritic cell migration would be connected with such a dramatic enhancement on clinical outcomes in our sufferers.”
Next, the researchers used a mouse model to identify how the tetanus booster enhanced dendritic cell migration to the lymph nodes. The outcomes recommended that providing a booster shot to mice that have obtained the tetanus vaccine triggered a recall reaction in the exposed T cells. Acting via a chemical messenger identified as CCL3, those T cells enhanced dendritic cell migration to the lymph nodes, which eventually improved the effect of the dendritic cell vaccine on tumor growth suppression.
Adding to above statment Dr. Mitchell said “Dendritic cell vaccines focusing on glioblastoma can be very effective by boosting migration of dendritic cells. We now understand how we may enhance results for patients obtaining this type of treatment”, more substantial clinical research have to be performed to ensure these outcomes.
In addition, more study is essential to determine the role of CMV in glioblastoma and to figure out mechanisms to boost efficacy of vaccines in cancer treatment.