Self-assembling nanovaccine
Currently, a promising area of cancer treatment with nanovaccines is actively developing. A good result was obtained in experiments, but widespread use is limited by the complexity of production and the impossibility of evaluating the effectiveness and safety of the method.
Researchers from the National Institute of Biomedical Imaging and Bioengineering in Bethesda, Maryland, USA, have developed a new technology that is based on the binding of an anti–cancer nanovaccine with albumin, a protein normally circulating in human blood. Albumin in this case plays the role of a supplier of nanocomplexes to the lymph nodes. As a result, you can get the desired result in the form of activation of the immune system against various types of tumors. The use of natural albumin for drug delivery is an important step towards the use of nanovaccines as a method of treating oncological diseases. Albumin is constantly present in the blood and is periodically filtered into the lymphatic system. Using it for transportation eliminates the need to create a component that would deliver the vaccine to its destination.
Nanovaccines consist of two components: the first is responsible for delivering the complex to the lymph nodes, the second directly activates immune cells to fight cancer cells.
Several nanovaccines have already been developed with various antigens – components that stimulate immune cells to attack certain types of tumors. To each antigen, the engineers added a blue dye molecule (Evans blue, EB), which binds to albumin in the body, forming the Albivax complex. Binding to albumin occurs almost immediately after injection into the blood. The complex was also enhanced with a small fragment of DNA, which plays the role of a "danger" signal and enhances the activation of immune cells, helping to achieve a more reliable result.
Scheme of self-assembly of the Albivax nanovaccine. A tumor-specific antigen and a DNA fragment are attached to the blue dye EB (marked with purple arrows). After injection into the blood, albumin (marked with green arrows) binds to EB and delivers the vaccine to the lymphatic system. DNA and antigen interact with immune cells (blue) in lymph nodes, where the antigen activates immune cells, and a fragment of DNA enhances this process. Source: Zhu et al.
The vaccines have been tested in several ways on different types of tumors.
In one experiment, healthy mice were injected with a nanovaccine against a thymus tumor three times at two-week intervals. After 70 days, seven of these immunized mice were injected with a large dose of tumor cells as a stress test. Four months later, five of them were still alive. These surviving mice were re-injected with a large dose of tumor cells. Four out of five mice survived after six months. The tests showed that four months after the last nanovaccine immunization, antibodies to thymus tumor cancer cells circulated in the blood of mice.
The Albivax nanocomplex has also been developed against colon cancer. In the experiment, mice were injected with human colon cancer cells that settled in various organs. Most often, these cells were retained in the lungs of mice. Thus, it was possible to create a model of aggressive colon cancer with metastases to the lungs. Six days after the tumor was detected in the lungs, the mice were injected with a nanovaccine. In addition, the mice received antibodies to the PD-1 protein, which, accumulating on the surface of cancer cells, suppresses the activity of the immune system. Nanovaccine in the presence of antibodies led to complete regression of lung tumors in six out of 10 mice within four months.
The sodium-phosphate buffer (1) and the control vaccine with a non-specific antigen (2) have no effect on the lung tumor of mice. The nanovaccine Albivax (3) significantly reduced the size of the tumor. The combination of Albivax and antibodies to PD-1 almost completely destroyed the tumor (4). Source: Zhu et al.
The authors of the study emphasize the long-term effect of Albivax: the antitumor activity of the immune system of mice persisted for six months after the introduction of the vaccine. For mice whose lifespan is about two years, this is quite a long time interval.
The use of albumin for drug delivery has been studied for 40 years. The binding of blue dye EB molecules to it makes the vaccine safer, and its use is a promising area of immunotherapy for oncological diseases. This albumin binding technology can be used in the molecular therapy of other diseases.
Article by Zhu et al. Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy is published in the journal Nature Communication.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to NIH materials: Engineers use natural protein as nanoshuttle for anti-cancer vaccines.