Anti-Tumor Immunotherapy for Brain Cancer
HMGB1 from Tumor Cells Activates TLR2 Signaling in Dendritic Cells
Jan 17, 2009
Glioblastoma Multiforme, or commonly called Glioblastoma, is a deadly type of a brain tumor. Of the 17,000 new brain tumor cases diagnosed in the USA each year, more than 50% of them are of the Glioblastoma type. The disease is characterized by atypical symptoms such as memory deficit, headache and vomiting. For an unknown reason, Glioblastoma affects males more than females.
Glioblastoma Tumors Are The Most Aggressive Brain Tumors
The survival rate of Glioblastoma patients is very low. Without treatment, the average survival time of patients is as low as 3 months and even treated patients often survive for only a few months. The tumors often become resistant to chemotherapy treatment which complicates treatment as normal brain tissues becomes easily damaged from increased doses of radiotherapy or chemotherapy.
New Therapeutic Approach to Attack Tumor Cells
Using a mouse model of Glioblastoma Multiform, a team of American researchers, led by Pedro R Lowenstein and Maria G Castro from The University of California and Cedars Sinai Medical Center, have developed a viral strategy able to stimulate the immune system to attack the brain tumor cells.
The study of the American researchers titled “HMGB1 Mediates Endogenous TLR2 Activation and Brain Tumor Regression” was published on January 13, 2009 in the scientific journal Plos Medecine (PLoS Med 6(1): e10 doi:10.1371/journal.pmed.1000010).
Dual Approach to Attacks Tumor Cells
The researchers developed a virus that carries a gene encoding for tyrosine kinase 3 ligand (or ftl3L) and for thymidine knase (or TK). Ftl3L is a protein known to attract a particular class of immune cells called dendritic cells while TK becomes a toxic protein in the cells when in presence of a drug called Gancyclovir.
When this virus was injected into the brain tumors of mice, the researchers observed a dramatic reduction of the tumor size. Interestingly enough, when the experiment was done in mice carrying tumor but lacking T lymphocytes, they did not observe a significant reduction of tumors or an improved survival of mice. T lymphocytes are an important subclass of white blood cells (See this article for more details on immune cells) involved in the immune response of the body.
Dying Tumor Cells Attracts Dendritic Cells That Activates T cells
More interestingly, the researchers discovered that tumors cells dying from the viral attack secreted a protein called HMGB1. This protein is specifically recognized by the receptor TLR2 present at the surface of another particular class of white blood cells called myeloid dendritic cells. The presence of HMGB1 attracts and activates the dendritic cells into the brain which, in turn, activate the T lymphocyte cells essential in killing other tumors growing in the brain.
New Treatment for Brain Tumors ?
While the effectiveness of such an immunotherapy approach still needs to be proven in humans as a potential treatment against cancer, this study presents a very elegant demonstration of using the specialized mechanisms of the immune system in conjunction with chemotherapy to deliver effective treatment against cancer. It would be interesting to know if such approach could ultimately be considered for the eradication of other types of cancer.
 |
 |
