12 April 2022

Gel with lymphocytes

Stanford scientists have developed a new method of delivering cancer drugs

Tatiana Matveeva, "Scientific Russia"

Engineers at Stanford University (USA) delivered modified immune cells to the tumor site by enclosing them in a hydrogel, the press service of the university reports. The results, published in the journal Science Advances (Grosskopf et al., Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors), showed that the new method helped to destroy the tumor in mice in 12 days. 

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The researchers combined immune T cells extracted from the body with a chimeric antigen receptor (CAR), and then added the resulting CAR-T cells and specialized signaling proteins (cytokines) into a hydrogel - a gel filled with water that shares characteristics with biological tissues - and injected the substance next to the tumor. This gel creates a temporary environment inside the body in which immune cells multiply and activate in preparation for the fight against cancer cells. The gel gradually releases activated CAR-T cells so that they can continuously attack the tumor. 

The gel consists of water and two ingredients: a polymer made of cellulose – the material contained in plants – and biodegradable nanoparticles. In combination, these two components bind to each other like a molecular "Velcro": they tend to stick together, but they are easy to break. This material can be injected through small needles, the authors note. At the same time, after injection, the "Velcro" is formed again and turns into a strong gel structure. 

The mesh configuration of the gel is woven tightly enough to prevent tiny cytokine molecules from slipping out. At the same time, the bonds of the structure are weak enough that CAR-T cells can break them and free themselves when they are ready to destroy cancer cells.

Having determined the best gel formula for cancer treatment, the research team tested their method on mice with tumors. They found that in all animals injected with a gel containing both CAR-T cells and cytokines, the tumor disappeared after 12 days. If there were only CAR-T cells in the hydrogel, in some mice the tumors disappeared more slowly or did not disappear at all. And if immune cells were injected into mice intravenously through a dropper or in a saline solution, rather than in a gel, the treatment was even less effective. In addition, the gel did not cause adverse inflammatory reactions in mice and completely decomposed in the body within a few weeks.

The team also tried to inject the gel further away from the tumor – on the opposite side of the mouse body from the cancer formation. Even in this case, the tumors in all animals still disappeared, although it took about twice as long as when injected next to the neoplasm.

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