An Artificial Lymph Node to Guide T Cells to Attack Specific Targets, Such as Cancers

Lymph nodes are points of coordination for the immune system, where T cells of the adaptive immune system are presented with antibodies that match target molecules, in effect given instructions as to what to attack next. Calling a structure made of biomaterials and decorated with antibodies an "artificial lymph node" does get the point across, but this is a far cry from, say, a lymph node organoid that shares a similar structure and set of cell populations with a natural lymph node. Still, the artificial structure does serve this one purpose, to instruct T cells. Researchers here envisage implanting a lymph node substitute as a part of a T cell therapy for cancer, using appropriate antibodies to ensure that the T cells will aggressively attack cancerous cells.

Lymph nodes - tiny glands throughout the body, mainly in the neck, armpits and groin - are part of the immune systems of mammals, including mice and people. They number in the hundreds so that immune cells in one area of the body don't have to travel far to alert the immune system to impending danger. "They are a landing spot where T-cells, the immune system's fighting cells, lay dormant, waiting to be activated to fight infections or other abnormal cells. Because cancers can trick T-cells into staying dormant, the artificial lymph node was designed to inform and activate T-cells that are injected alongside the lymph node."

To create the artificial lymph node, the scientists used hyaluronic acid, a substance found naturally in the body's skin and joints. Because of its properties, hyaluronic acid is often used in biodegradable materials such as wound healing patches meant to be implanted or applied to the body. Among those properties, hyaluronic acid can connect with T-cells via a cell surface receptor. Researchers used hyaluronic acid as the scaffolding, or base, for their new lymph node, and added MHC (major histocompatibility complex) or HLA (human histocompatibility antigen) molecules, which rev up T-cells and other immune system components. Then, they also added molecules and antigens common to cancer cells to "teach" T-cells what to look for.

"By adding different antibodies to the artificial lymph node, we have the ability to control what the T-cells are being activated to search for. An advantage to this approach over other cell-based therapies such as CAR-T is fewer manufacturing steps. Current cell-based therapies require extracting T-cells from a patient, manipulating them outside of the body to recognize a particular type of cancer, and injecting them back into the patient. In our approach, we inject T-cells along with an artificial lymph node, and the T-cells get primed and educated by the artificial lymph node inside of the body. Then, the T-cells can travel anywhere to destroy cancer cells."



Lygenesis is a company perfectly situated to make such an cell therapy.

Posted by: Rebel Ruby at June 14th, 2024 10:13 AM

Some similar work at the Wyss institute:

"Now, a research team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) has developed a simple intervention in the form of a biodegradable scaffold material that can be locally injected under the skin and used to restimulate CAR-T cells after their administration to increase their therapeutic efficacy. In mice that developed an aggressive blood tumor and were treated with a non-curative dose of CAR-T cells, the team's "T-cell enhancing scaffolds" (TES) significantly curbed tumor growth and prolonged the animals' survival. The improved therapeutic efficacy of the CAR-T cells was due to TES' ability to increase the numbers of CAR-T cells in the blood circulation, as well as steer their differentiation into tumor-killing subtypes of T cells."

Posted by: jimofoz at June 17th, 2024 12:50 PM

Also from the Wyss recently:

"While researchers have studied the early expansion of LNs following vaccination, they have not investigated whether prolonged LN expansion could affect vaccine outcomes.

Now, for the first time, researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and Genentech, a member of the Roche Group, found a way to enhance and extend LN expansion, and study how this phenomenon affects both the immune system and efficacy of vaccinations against tumors. Key to their approach was a biomaterial vaccine formulation that enabled greater and more persistent LN expansion than standard control vaccines. While the oversized LNs maintained a normal tissue organization, they displayed altered mechanical features and hosted higher numbers of various immune cell types that commonly are involved in immune responses against pathogens and cancers. Importantly, "jump-starting" lymph node expansion prior to administering a traditional vaccine against a melanoma-specific model antigen led to more effective and sustained anti-tumor responses in mice."


"In a recent paper published in Nature Biomedical Engineering, the researchers demonstrated that by attaching disc-shaped microparticles called "backpacks" to neutrophils, they could switch the cells into their anti-tumor (N1) state and keep them in that state. When these treated neutrophils were infused into mice with cancer, they activated other immune cells against the disease, including natural killer (NK) cells and T cells. Treated mice had smaller tumors and lived longer than untreated mice, and the results were even better when the backpack-bearing neutrophils were combined with common "checkpoint inhibitor" cancer drugs."

Posted by: jimofoz at June 17th, 2024 1:23 PM
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