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In a proof-of-principle study in mice, scientists at Johns Hopkins Medicine announced the creation of a specialized gel that acts as a lymph node to successfully activate and multiply immune system T cells that fight cancer . The work will bring scientists closer, they say, to the injection of such artificial lymph nodes in humans and stimulation of T cells to fight the disease.
In recent years, a wave of discoveries has developed new techniques for using T-cells, a type of white blood cell, in the treatment of cancer. To be successful, cells must be sensitized, or taught, to detect and react to the molecular flags that cover the surface of the cancer cells. The work of educating T cells this way usually occurs in the lymph nodes, small bean-shaped glands that are found all over the body that houses T cells. But in patients with cancer and immune system disorders, this learning process is failing or does not occur.
To remedy these abnormalities, current T-cell-based booster therapy requires doctors to remove T-cells from the blood of a cancer patient and re-inject them into the patient's cells after genetic engineering or Activation of cells in a laboratory to recognize cancer. linked molecular flags.
One of these treatments, called CAR-T therapy, is expensive and available only in specialized centers with laboratories capable of carrying out the complex task of engineering T lymphocytes. Moreover, T cell culture in the laboratory usually takes place. six to eight weeks and, once reintroduced into the body, the cells do not last long in the patient's body. The effects of the treatment can therefore be short-lived. .
The new job, reported on April 10 in the newspaper Advanced Materials, is an attempt by Johns Hopkins scientists to find a more efficient way of engineering T cells.
"We think the environment of T cells is very important, biology does not occur in plastic dishes, it occurs in tissues," says John Hickey, Ph.D., a candidate in biomedical engineering at the University of Toronto. Johns Hopkins University School of Medicine and first author of the study report.
To make environmental T-cell techniques more biologically realistic, Hickey – in collaboration with his mentors Hai-Quan Mao, Ph.D., badociate director of the Johns Hopkins Institute of NanoBioTechnology and Jonathan Schneck, MD, Ph.D., professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine – attempted to use a jelly-like polymer, or hydrogel, as a flat For the hydrogel, scientists have added two types of signals that stimulate and "teach" T cells to target foreign targets to destroy.
In their experiments, hydrogel-activated T cells produced 50% more molecules called cytokines, an activation marker, than T cells stored in plastic culture dishes.
As hydrogels can be made to order, Johns Hopkins scientists have created and tested a range of hydrogels, ranging from the very soft touch of a cell to the stiffer quality of a crowded lymph node. of cells.
"One of the surprising discoveries is that T cells prefer a very mild environment, similar to interactions with individual cells, as opposed to a very dense tissue," says Schneck.
More than 80% of the T cells on the soft surface grew, compared to none of the T cells on the firmer hydrogel type.
When the Johns Hopkins team put T cells on a soft hydrogel, they found that T cells only multiplied from a few cells to about 150,000 cells – a sufficient amount for cancer treatment – in the seven days. In contrast, when scientists used other conventional methods to stimulate and develop T cells, they were able to culture only 20,000 cells in seven days.
In the next series of experiments, scientists injected T-cells made in soft hydrogels or plastic culture dishes into mice with melanoma, a deadly form of skin cancer. Tumors in mice with T cells grown on hydrogels remained stably sized, and some of the mice survived beyond 40 days. In contrast, tumors developed in most mice injected with T cells grown in plastic boxes, and none of these mice lived for more than 30 days.
"As we refine the hydrogel and reproduce the essential characteristics of the natural environment, including the chemical growth factors that attract T cells to fight cancer and other signals, we finally we can design artificial lymph nodes for therapy based on regenerative immunology "says Schneck, a member of the Johns Hopkins Kimmel Cancer Center.
Scientists have filed patents relating to the hydrogel technology described in their report.
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