Double-tipped arrow
Researchers at the University of Virginia School of Medicine, working under the guidance of Dr. Jogender Tushir-Singh, have developed a powerful approach to the treatment of ovarian cancer based on the use of antibodies. The authors hope that it will help overcome the difficulties faced by the developers of immunotherapy for solid tumors.
Immunotherapy of malignant tumors is a very promising and actively developed area of modern oncology. However, in the case of ovarian cancer, as well as a number of other solid organs, researchers are faced with the fact that modified immune cells injected into patients are unable to effectively infiltrate the tumor bed. During the experiments, the authors found that this is partly due to the properties of the tumor microenvironment: severe hypoxia (oxygen deficiency), anergicity of T-lymphocytes (lack of reaction to foreign substances) and, which is especially characteristic of ovarian tumors, a protective barrier formed around tumor cells by unusually large receptors. All this makes it difficult for therapeutic antibodies to penetrate, triggering the process of destroying a cancer cell or attracting immune cells to it, to their targets – the surface proteins of malignant cells.
To solve this problem, the authors have developed antibodies, which they compare to a "two-tipped arrow". One of the targets of these antibodies is the folic acid receptor-alpha-1 (FOLR1), which is characterized by high expression on ovarian cancer cells. This protein is used by antibodies as an anchor anchoring them in tumor tissue. The second target, death receptor 5, when bound to a therapeutic antibody triggers the mechanism of apoptosis - programmed cell death.
Based on the results of laboratory experiments on cell lines and mice, the researchers concluded that the effectiveness of the antibodies they created is more than 100 times higher than the antibodies previously tested in clinical trials of ovarian cancer therapy.
Moreover, the new antibodies avoid the toxicity associated with the use of earlier antibody-based drugs. Traditional antibodies leave the bloodstream too quickly and accumulate in the liver, having a toxic effect on hepatocytes. The new approach ensures the fixation of antibodies in the tumor tissue and prevents the development of hepatotoxicity.
To date, the method is in the early stages of development, but the authors plan to test it in clinical trials over time.
Article by Gururaj Shivange et al. A Single-Agent Dual-Specificity Targeting of FOLR1 and DR5 as an Effective Strategy for Ovarian Cancer is published in the journal Cancer Cell.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on University of Virginia School of Medicine: UVA Developing 'Two-Headed Arrow' to Kill Ovarian Cancer.