Thallium against cancer
A new Russian cancer drug has successfully passed preclinical trials
Arina Petrova, Hi-tech+
This is the first domestic drug using a vector nanosomal targeted delivery system.
The Biotechnology company has developed and conducted preclinical trials of an innovative delivery system and the newest drug for the treatment of malignant tumors. The principle of action of the drug is based on the targeted delivery of the active substance to the tumor cell – this helps to avoid side toxic effects on the body, characteristic of most drugs that are used in oncotherapy.
The active substance of the new drug is the salt of the chemical element thallium. For the treatment of malignant neoplasms, these compounds have not been used before, since in their pure form they have a pronounced toxic effect on all cells of the body. A chemically modified bacteriophage MS2 is used as a means of delivery. Thallium salt is placed inside the bacteriophage and in this form is delivered to the tumor cell, where it is released during phagocytosis.
Monovalent thallium salts were chosen because they have a strong cytotoxic effect, to which resistance does not arise, while their targeted delivery provides a toxic effect only on tumor cells. The effectiveness of the cytotoxic action of monovalent thallium salts is due to the fact that when they enter the cell, firstly, they are not excreted by drug-resistant proteins and, secondly, they trigger various apoptic reactions. Thus, it allows you to activate the process of death of these cells, block further tumor growth and stop the spread of cancer cells (metastasis).
At the same time, due to the targeted delivery of thallium, its toxic effect on the body as a whole is minimized. A bacteriophage shell coated with iRGD peptides helps deliver thallium precisely to the cancer cell. On the surface of tumor vessels there are special substances-integrins – aB3B5-molecules to which the bacteriophage adheres, resulting in the release of thalia into the cell. This is a unique technique that is used for the first time in the world of oncotherapy.
"One of the methods of treatment of most types of oncological diseases today is considered chemotherapy – explains Elena Grigorieva, Head of the Laboratory of Radionuclide and Radiation Technologies in Experimental Oncology at the Research Institute of Clinical and Experimental Radiology. "But the problem is that classical chemotherapy has reached the limit in its development, because it is associated with a huge number of side effects that complicate treatment and worsen the quality of life of patients."
More progressive monoclonal therapy also has its own barriers, since it involves the creation of separate drugs for each type of cancer, and this is very expensive. According to the director of the company "Biotechnology" Andrey Vologda, for this reason, it was decided to focus on the development of targeted methods of delivery of chemotherapeutic drugs: on the one hand, they minimize the toxic effects of active substances on the body, and on the other hand, they are much cheaper than monoclonal antibodies.
During preclinical animal trials, the effectiveness of the drug was assessed as high. The next step in the development is to obtain permission from the Ministry of Health to conduct the first stage of human clinical trials. If all the stages of testing are successful, the drug will be put into mass production – approximately this will happen in 2025.
The bacteriophage, which is part of the drug, can also be used to carry other substances in the treatment of other nosologies. This method has already been tested at Rosatom by placing radioisotopes in the bacteriophage "BioTechnology". As a result, the integrity of the bacteriophage was preserved, which indicates the possibility of using this method in the development of other drugs. And after improvements in the part of iRGD peptides covering the shell of the bacteriophage, the drug can be used as a universal remedy for the treatment of solid cancer.
"Targeted delivery is one of the most promising areas in the treatment of malignant neoplasms, and bacteriophage "BioTechnology" opens up broad prospects for the use of this method," says Roman Sharov, head of the R&D project office of JSC "V/O "Isotope" (part of JSC "Rusatom Healthcare is a single integrator in the field of radiation technologies for medicine and industry in the contour of the Rosatom State Corporation) – We hope that Rosatom's participation in this project will help to cope with one of the most difficult problems in oncology – to find a method of effective and least toxic treatment for even the most so-called unpromising patients. Now we are considering the possibility of becoming a distributor of the drug after its release – both domestically and on the international market."
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