Stem cells with herpes virus against brain cancer
Stem cells loaded destroying malignant cells particles of the herpes virus attacking a brain tumor. Tumor cells are colored in green, loaded with particles of the herpes virus stem cells – red, and infected with the herpes virus tumor cells yellow.
Researchers at the stem cell Institute, part of the Harvard University, offer a promising method of increasing the effectiveness of oncolytic viruses. They argue that the application of a gel containing viral particles loaded stem cells in tissue exposed when you remove tumors, significantly improves survival of mice with glioblastoma multiforme, the most common and most difficult-to-treat malignant brain tumor in adults.
The effectiveness of therapy using oncolytic viruses was analyzed in multiple clinical trials phase 1 and phase 2 involving patients with cancer of the brain. Unfortunately, these studies did not bring the expected success. In preclinical experiments looked the most promising oncolytic strains of herpes simplex virus with the ability to infect dividing cells of the brain. However, clinical application of these strains was not effective enough because the researchers failed to ensure the presence of viral particles in the tumor area for a prolonged period of time necessary to obtain positive results of therapy.
Authors working under the guidance of Dr. Khalid Shah (Khalid Shah), I decided to use as carriers of oncolytic viruses mesenchymal stem cells isolated from bone marrow. A distinctive feature of these cells that can give rise to various types of tissues, is their low immunogenicity, that is, the inability to cause a full-blown immune response in the recipient's body.
Mesenchymal stem cells were loaded with particles of the herpes virus, after which they entered into glioblastomas formed in the brain of experimental mice. The use of multiple imaging markers have allowed researchers to observe viral particles as they move from stem cells to the surface of the tumor and, subsequently, into the tumor focus.
According to the authors, 70-75% of patients with glioblastoma multiforme carried out a surgical operation to remove the tumor focus. Earlier experiments in a mouse model of this surgical intervention has demonstrated that the introduction of encapsulated in biocompatible gels mesenchymal stem cells to the area of tumor removal is a promising therapeutic approach. Based on these data, the authors encapsulated particles loaded with oncolytic herpes virus-derived mesenchymal stem cells in a biocompatible gel and caused the resulting material on the fabric, exposed with the removal of the tumor.
Comparison of the results obtained with the direct introduction of therapeutic cells into the tumor, and if you make containing gel to the area of tumor removal showed that the gel provides a more prolonged cell viability and prevent leaching of cerebrospinal fluid. This allowed the virus particles to replicate and destroy individual cancer cells that remain after removal of the primary tumor focus (residual cells), and provided higher survival rate of mice that underwent therapy is encapsulated in the gel cells.
The authors also noted that they carried out the experiments indicate a failure of the "bare" particles of the herpes virus to destroy residual tumor cells. This partly explains not very impressive results of clinical trials of therapy of oncolytic viruses without the use of stem cells as carriers.
Another drawback to the therapy of oncolytic viruses is immune to some types of brain tumors. To resolve this problem, scientists have created a strain of the herpes virus expressing oncolytic agent for more TRAIL. Experiments in a mouse model of glioblastoma, created from human tumor cells resistant to herpes simplex virus, also showed an improved survival rate.
The authors note that the adaptation of the proposed approach for the treatment of breast cancer, lung and skin, often metastasizing to the brain, require additional pre-clinical studies. At the same time, they hope that the clinical trials proven their option of therapy will begin within the next 2-3 years.
Article Duebgen Matthias et al. Stem Cells Loaded With Multimechanistic Oncolytic Herpes Simplex Virus Variants for Brain Tumor Therapy published in the Journal of the National Cancer Institute.
Eugene Ryabtsev
The portal of "Eternal youth" http://vechnayamolodost.ru according to the materials of Harvard University:
Herpes-loaded stem cells used to kill brain tumors.
20.005.2014