In a study published in the March 15 issue of The Journal of Immunology, researchers at Board of Governors' Gene Therapeutics Research Institute at Cedars-Sinai Medical Center have developed a way to overcome immune privilege in the brain to eradicate potentially deadly brain tumors such as glioblastoma multiforme and other types of brain infections.
Brain tumors account for 85 to 90 percent of all primary central nervous system tumors. Of those tumors, almost 40 percent are either the deadly glioblastoma multiforme or anaplastic astrocytomas. Each year about 19,000 people in the United States are diagnosed with primary brain cancers, and close to 70 percent of those diagnosed will not survive more than five years. In addition, approximately 150,000 Americans a year are diagnosed with metastatic brain tumors, cancer that has spread into the brain from another part of the body.
"We have developed a novel gene therapy strategy to modify the brain microenvironment which will allow us to overcome immune privilege in the brain and improve the lives of those who are suffering with life-threatening diseases such as brain cancer or brain infections," said Maria Castro, Ph.D., co-director of the Board of Governors' Gene Therapeutics Research Institute at Cedars-Sinai Medical Center and the principal investigator of the study.
The brain's blood-brain barrier and lack of a drainage system means that the organ has immune privilege and therefore cannot mount a defense against cancer or other infectious diseases localized in it. Once activated, immune cells can cross the blood-brain barrier and attack pathogens or tumors; however, it is not possible to mount an effective immune response from the brain itself because it lacks antigen presenting cells. In the study published in the Journal of Immunology, researchers lead by Dr. Castro and Dr. Pedro Lowenstein found a way of engineering the brain's microenvironment to induce the migration of antigen presenting cells to the brain itself and mount an effective immune response against deadly tumors and other brain infections.
In a prior study published in Cancer Research in 2005, the same Cedars-Sinai researchers tested two genes, one that killed cancer cells and a second that elicited the production of immune cells in a large brain tumor model in laboratory mice. Now, building upon that study, these scientists, using a viral vector that delivers the protein Flt3 Ligand into the brain, have demonstrated that it attracts immune cells which can take up tumor antigens and present them to the immune system. These dendritic cells, also referred to as antigen presenting cells, which normally are absent from a healthy brain, can destroy tumors as well as combat any other type of brain infections.