Johns Hopkins University School of Medicine researchers have developed an artificial lymph node that fights cancer, according to a new study conducted in mice and published in the scientific journal Advanced Materials (“Artificial Lymph Node’ Used to Treat Cancer in Mice“).
T cell “Schoolhouse”
The new artificial lymph node – a sac filled with immune system ‘components’ – is implanted under the skin and is designed to act as a ‘school’ that teaches the immune system’s T cells to recognize and destroy cancer cells.
The valuable role of lymph nodes
Lymph nodes – tiny glands scattered throughout the body but most commonly found in the neck, armpits and groin – are part of the immune system of mammals, including mice and humans. There are hundreds of such glands throughout the body so that immune cells in one area of the body do not have to travel far to alert the immune system to an impending danger in another distant area of the body.
T cell signaling and activation
“Lymph nodes are the ‘nest’ where T cells, the main warriors of the immune system, remain dormant, waiting to ‘wake up’ when they need to deal with infections or other abnormal cells,” explained Dr. Natalie Livingston, first author of the new of the study, a postdoctoral researcher at Massachusetts General Hospital, and added: “Cancers can ‘trick’ T cells into remaining dormant. Our artificial lymph node is therefore designed to inform and activate the T cells that are injected with it into the body.”
Using hyaluronic acid
To create the artificial lymph node, the scientists used hyaluronic acid – this moisturizing substance that is now well-known for its use in cosmetics and cosmetic medicine, and which is found naturally in the skin and joints. Thanks to its properties, hyaluronic acid is often used in biodegradable materials such as wound and wound healing patches that are injected into the body or applied to the skin. Among its other properties hyaluronic acid has the ability to bind to T cells through a receptor on the cell surface.
In a previous study published in 2019 (“Scientists Advance Creation of ‘Artificial Lymph Node’ to Fight Cancer, Other Diseases“), Johns Hopkins researchers led by Johns Hopkins University School of Medicine professor of Pathology, Medicine and Oncology and director of the Johns Hopkins Center for Translational Immunoengineering Jonathan Schneck showed that hyaluronic acid increases activation of T cells.
The mold and its contents
In the new study, the research team used hyaluronic acid as a template, as a mold to create the lymph node, and added to this mold genes of the Major Histocompatibility Complex (MHC, a set of closely related genes that play an important role in the immune response). and antigens of the HLA system (Human Leukocyte Antigens, a set of antigens which help the immune system recognize and distinguish its own cells from foreign ones). They also added molecules and antigens found on cancer cells to “train” T cells to seek out cancer cells to fight them. “By adding different antibodies to the artificial lymph node, we gain the ability to control the activation of T cells as well as the target of this activation,” noted Dr. Livingston.
Twice as wide as a human hair
The Johns Hopkins experts’ artificial lymph node is about 150 micrometers in size (almost twice the width of a human hair). It is small enough to remain under the skin without problems and at the same time large enough not to be carried away in the bloodstream.
The advantage compared to cellular therapies
“One advantage of this approach compared to cell-based cancer therapies such as CAR-T is that it requires fewer manufacturing steps,” said Professor Schneck. Existing cell therapies require extracting the patient’s T cells, processing them outside the body to recognize a specific form of cancer, and reinfusing them back into the patient’s body. “In our approach, the T cells are injected together with the artificial lymph node and are trained inside the body by the lymph node about what to look for. The T cells can then travel anywhere to destroy the cancer cells,” noted the professor, who led the researchers in the new study along with Hai-Quan Mao, director of the Johns Hopkins Institute for Nanobiotechnology.
The mouse experiment
The research team conducted experiments using the artificial lymph node in mice that were given melanoma (the most aggressive skin cancer) and colon cancer. Six days after the tumors were implanted, the artificial lymph node as well as T cells were introduced into the experimental animals.
The mice that received the artificial lymph node were compared with three other groups of mice: the first received only the artificial lymph node, the second only T cells (which had not been activated by the artificial lymph node) while the third received T cells in combination with anti- -PD-1.
Encouraging results
Nine days later the mice with melanoma and colon cancer that received the combination of the artificial lymph node, T cells and anti-PD-1 drug showed the best survival rates (three of seven animals remained alive 33 days after implantation of tumors) compared to the other groups of mice that lived up to about 26 days. This particular group of mice also showed the slowest tumor growth – it took five to 10 days longer for their cancers to double in size than the other groups of experimental animals.
The “immunologically active nest”
The researchers also discovered that the artificial lymph node also attracted many other immune cells – acting as an “immunologically active nest” which provided further activation of the immune system. Furthermore, when the mice were injected with T cells along with the artificial lymph node, they multiplied much more (up to nine times more).
Bypassing dendritic cells
Dr Livingston explained that the new approach is different from a cancer vaccine that activates dendritic cells – helper cells of the immune system that teach T cells who the ‘enemies’ are that they are called upon to eliminate. Cancer patients often develop dysfunctional dendritic cells, so it is important that the artificial lymph node bypasses dendritic cells and directly activates T cells.
The next step is to “recruit” more immune cells
The next step for the researchers is to conduct further laboratory studies in which they will add other marker molecules to the lymph node so that it “recruits” more immune cells.
A kind of “living medicine”
“We have ‘married’ materials science with immunology to create a potential therapy that creates its own immune community – it’s a kind of living medicine,” concluded Professor Schneck.
The researchers have already filed for a patent on this promising technology.
