Double-acting virus
Researchers at the University of Oxford, working under the leadership of Dr. Kerry Fisher, armed the carcinoma cell-killing virus with a protein that ensures the destruction of surrounding cells used by the tumor to protect against the immune system.
Carcinomas are the most common solid malignant tumors that develop from skin cells, as well as tissues lining or covering internal organs such as the pancreas, rectum, lungs, mammary glands, ovaries and prostate. Tumors of this type surround themselves with fibroblasts, which not only protect them from the immune system, but also produce the necessary tumor growth factors and nutrients. Even with the destruction of most of the tumor cells, fibroblasts protect residual (residual) cancer cells from the immune system and contribute to the recurrence of the tumor.
To date, all methods aimed at destroying such tumor-associated cells can lead to the death of fibroblasts throughout the body, including in the bone marrow and skin, which is fraught with serious side effects.
The authors proposed using a modified well-known oncolytic virus enadenotucirev, which is already undergoing clinical trials as a means of carcinoma therapy, to eliminate these cells. Initially, this virus was created for the selective destruction of malignant cells.
Additional instructions were added to the genetic material of the virus, forcing infected tumor cells to produce a protein known as a bispecific activator attracting T cells. This protein binds two types of cells together. In this case, one end of it is attached to the surface of the fibroblast, and the other to the surface of the T–lymphocyte, whose main function is the destruction of defective cells. As a result, the T-lymphocyte activated in this way kills the fibroblast connected to it.
The new approach provides simultaneous destruction of cancer cells and tumor-associated fibroblasts. This will reduce the severity of carcinoma-induced suppression of the immune system and trigger a normal antitumor immune response.
The researchers have already successfully tested their method on mice, as well as fresh biopsy material of tumors obtained from patients who signed informed consent. In addition, testing was carried out on samples of healthy bone marrow, the results of which demonstrated the absence of toxicity and inadequate activation of T-lymphocytes.
Given that this virus is already undergoing clinical trials, the authors hope that they will be able to start clinical trials of its new modification at the beginning of next year.
Article by Joshua D. Freedman et al. An Oncolytic Virus Expressing a T-cell Engager Simultaneously Targets Cancer and Immunosuppressive Stromal Cells is published in the journal Cancer Research.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Medical Research Council: New dual-action cancer-killing virus.