Gene therapy for the treatment of brain cancer
Scientists at Cedars-Sinai Medical Center, working under the guidance of Dr. Maria Castro, have tested a new treatment method on a newly developed rat model of polymorphic glioma. Based on the results obtained, they plan to start clinical trials of the method this year.
Polymorphic glioma, the most common aggressive type of brain cancer, usually kills its victims within 6-12 months of diagnosis. Patients with polymorphic glioma often develop behavioral abnormalities that disrupt memory, sense of balance and ability to concentrate attention. The reason for this lies in the fact that growing tumors displace and compress nerve endings and axons conducting nerve impulses.
Tumors of this type are very difficult to destroy for a number of reasons. Polymorphic glioma grows very quickly and reaches very large sizes by the time of diagnosis. In addition, glioma cells actively infiltrate surrounding tissues and migrate to other regions of the brain, excluding the possibility of complete surgical removal. Chemo- and radiotherapy also do not ensure the destruction of residual cells, which often acquire resistance to treatment. The effectiveness of chemotherapy at the same time reduces the blood-brain barrier, and immune cells necessary for the formation and maintenance of a systemic antitumor immune response are usually not found in brain tissues.
The new method of gene therapy makes it possible to overcome all these difficulties. To transfer genes encoding two therapeutic proteins directly into tumor cells, scientists used an adenovirus devoid of pathogenic genes. One of the therapeutic proteins, the FMS-like tyrosine kinase-3 ligand (FMS like tyrosine kinase 3 ligand, Flt3L), is designed to attract dendritic cells to the tumor zone. The second therapeutic protein – thymidine kinase of herpes simplex virus type 1 (herpes simplex virus type 1 thimidine kinase, HSV1-TK) – in combination with the antiviral drug gancyclovir (GCV) destroys tumor cells.
Dendritic cells purify tissues from fragments of dead cells and in the process of their processing notify the immune system of the presence of foreign substances or antigens in the body, in this case, tumor cells. Immune cells that are familiar with the antigens move into the tumor zone and destroy malignant cells.
As part of an earlier work, the authors tested the effectiveness of the individual use of HSV1-TK and ganciclovir for the treatment of polymorphic glioma. In both cases, the survival rate of the animals exceeded the survival rate of the control group by 20%. The addition of Flt3L stimulating the activity of dendritic cells to the protocol increased the survival rate to about 70%. At the same time, systemic immune activity was maintained even with the introduction of additional tumor cells into the body. In addition, the authors state that such combination therapy also eliminates behavioral disorders caused by tumor growth.
The developers believe that in the near future the proposed method of gene therapy can be used as an addition to traditional methods of treatment, which will reduce the doses of chemotherapy drugs and radiation exposure and avoid the development of side effects.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
27.02.2008