23 April 2019

Gel lymph node

Johns Hopkins University researchers have developed a specialized hydrogel that simulates the structure of the lymph node and ensures the successful activation and reproduction of immune cells specific to malignant tumors.


T-lymphocytes develop in a transparent gel.

In recent years, researchers have been actively developing methods for the use of T-lymphocytes in cancer therapy. For successful treatment, such lymphocytes need to be "trained" to recognize the molecular markers of malignant cells and respond to them. Usually, the training of T-lifmocytes occurs in the lymph nodes – small bean-shaped glands scattered throughout the body. However, in patients with malignant tumors and diseases of the immune system, this learning process is either disrupted or does not occur at all.

To date, to compensate for this defect, T-lymphocytes are isolated from the patient's blood and injected back after genetic modification or activation of cells in the laboratory, after which they begin to recognize the molecular labels of cancer cells.

One type of such therapy, known as CAR-T therapy, is very expensive and is available only in specialized centers with specially equipped laboratories. In addition, it requires 6-8 weeks of cultivation of T-lymphocytes, and after administration to the patient, the cells live very short, which causes the short-term effects of therapy.

The technology developed by the authors can help in solving this problem. Their work was based on the belief that the environment is very important for the proper activation of T-lymphocytes. For a more realistic reproduction of the microenvironment of T-lymphocytes, the researchers used a gel-like polymer, on the surface of which two compounds were applied that stimulate the activation of these cells.

During the experiments, hydrogel-activated T lymphocytes produced 50% more cytokines indicating their activation than cells cultured in plastic Petri dishes.

Also, as part of the work, the authors tested a whole range of hydrogels with different densities, ranging from very soft, corresponding to the interaction of lymphocytes with single cells, and ending with a very dense, simulating a lymph node densely packed with cells. Unexpectedly for them, it turned out that T-lymphocytes prefer a softer environment, in which about 80% of cells were divided. At the same time, on the densest hydrogel, T-lifocytes stopped dividing altogether.

When cultured on a soft hydrogel after 7 days, several cells formed a population of about 150,000 T-lymphocytes, which is enough for antitumor therapy. For comparison, traditional cultivation methods make it possible to obtain no more than 20,000 T-lymphocytes from a similar number in a 7-day period.

At the next stage of the work, the researchers injected T-lymphocytes modified on soft hydrogel and in Petri dishes to mice with implanted melanomas. Tumors of mice injected with hydrogel-cultured T lymphocytes did not increase in size, and some mice lived for more than 40 days. At the same time, in most animals that were injected with T-lymphocytes cultured in Petri dishes, tumors continued to grow, and none of them lived more than 30 days.

According to the authors, eventually they hope, by improving the hydrogel and reproducing important parameters of the natural microenvironment, including chemical growth factors and other signals, to learn how to create artificial lymph nodes for regenerative immune therapy of malignant diseases.

Article by John W. Hickey et al. Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy is published in the journal Advanced Materials.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on Johns Hopkins Medicine: Scientists Advance Creation of 'Artificial Lymph Node' to Fight Cancer, Other Diseases.

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