Antitumor platelets

A new method of delivery of antitumor drugs has been developed

Anna Stavina, XX2 century

After the operation to remove a malignant tumor – even if the surgical intervention itself was considered successful – it is impossible to make sure that all the micro-tumors are also removed. The risk of a possible relapse is a serious cause for concern.

However, it is known that platelets, blood plates that play an important role in wound healing, immediately rush to the site of the operation through the blood vessels. And what if platelets will carry antitumor agents for the destruction of micro-tumors? Researchers from the University of North Carolina at Chapel Hill (University of North Carolina at Chapel Hill) and the University of North Carolina (North Carolina State University) have asked this question and have already developed a way to deliver drugs using blood plates. The new system has been successfully tested on animals. The results of the study are published in Nature Biomedical Engineering (Wang et al., In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy).

"The interest in developing strategies to prevent cancer recurrence is huge," says lead author Zhen Gu, who works both at Chapel Hill University and at the state University. – On the other hand, deserved attention is now focused on the immunotherapeutic approach to the fight against cancer. But immunotherapy drugs do not attack the tumor directly, they use the body's immune system to destroy cancer cells."

However, immune cells can be blocked by inhibitor molecules. Tumor cells produce them to "turn off" the immune response. Special drugs called immune checkpoint inhibitors can help in overcoming the protective mechanisms of the tumor. These include, for example, anti-PD-1/PD-L1 monoclonal antibodies.

"But the problem of the effectiveness of the use of these antibodies in the treatment of patients persists," explains senior author of the study Chao Wang (Chao Wang). – To date, there are difficulties with the delivery of drugs to the site of localization of the tumor. If the antibodies start to "miss" or their doses are too high, the patient may develop serious side effects, such as autoimmune diseases that damage healthy tissues."

To solve these problems, Gu and his colleagues decided to target immunotherapeutic drugs directly at the micro-tumors remaining in the body after the removal of the main neoplasm. To do this, the researchers developed a mechanism that allows the drugs to attach to the surface of inactive platelets and move with them through the blood vessels to the site of the surgical wound.

First, scientists attached antibodies – the active ingredient of an immunotherapy drug – to the surface of platelets in vitro. This was done using a special molecular "glue" based on maleic acid imide. The use of "glue" saved the researchers from the need to genetically modify the blood plates. Then the platelets carrying the medicine were injected into the body by intravenous injection. Moving through the blood vessels, platelets independently moved to the wound site, where they were activated.

At the moment of platelet activation, microparticles carrying antibodies were detached from its surface. These microparticles were formed from the platelet cell membrane. When released, they found themselves in the immediate vicinity of the place where the tumor was located, and where micro-foci of the disease may have remained.

Figure from an article in Nature Biomedical Engineering – VM.

For experiments, scientists used model animals. In some mice, the development of melanoma was provoked, in some – triple negative breast cancer. Then the animals underwent surgery to remove the tumor and immunotherapy using a new technique. Anti-PD-L1 antibodies were used as a drug (atezolizumab, trade name Tecentriq, not registered in Russia).

Mice treated with atezolizumab lived "significantly" longer than animals treated with placebo. According to Gu, this effect was due to a reduction in the risk of tumor recurrence and metastasis.

"This technology is designed to treat different types of oncological diseases. Therefore, we investigated its effectiveness, including on the leukemia model," says Gu. – Leukemia is a "liquid" form of cancer, it circulates in the blood, while melanoma and breast cancer are dense (or, as doctors say, solid) tumors. The range of application of the new approach will be very wide."

Portal "Eternal youth" http://vechnayamolodost.ru  03.02.2017