Nat Biotech: New implantable stent more effective than CAR-T therapy

Researchers at the University of North Carolina at Chapel Hill and North Carolina State University have developed an implantable scaffold that releases CAR-T cells to attack tumors

T cells are part of the immune system whose job is to recognize and destroy cells in the body that have been infected by invading pathogens

"A major disadvantage of CAR-T cell therapy is that it is very expensive—hundreds of thousands of dollars per dose," said corresponding author Yevgeny Brudno

"Many people are excluded from this treatment

To address this challenge, the researchers developed an implantable scaffold called a multifunctional alginate scaffold for T cell engineering and release (MASTER)

Before understanding the principle of MASTER, you must understand how CAR-T cells are generated

First author Pritha Agarwalla, a postdoctoral researcher in the Joint Department of Biomedical Engineering, said: "Our MASTER technology transfers the tedious and time-consuming steps of activation, reprogramming and amplification to the patient

MASTER is a biocompatible sponge-like material that looks a bit like cotton candy

After implantation, the cell activation process continues

"The MASTER material has properties similar to that of a sponge, allowing viruses and cells to bind tightly together, facilitating genetic reprogramming," Agarwalla said

"When engineering this material, the key was to keep it dry and take up the mixture of T cells and virus," Brudno said.

In these studies, the researchers used mice with lymphoma

"Our technology is performing very well," Brudno said

In addition, because cells are implanted within hours of isolation, fewer manipulations mean healthier cells

"The end result was that mice treated with CAR-T cells through MASTER were much better at fighting tumors than mice treated with conventional CAR-T cells," Agarwalla said

"MASTER technology is promising in liquid tumors such as lymphomas, but we're more eager to see its performance in solid tumors, including pancreatic and brain cancers," Brudno said

“We are working with industry partners to commercialize this technology, but there is still a lot of work to be done before clinical application
.
Further research work is necessary before we start trying clinical trials in human patients, in animal models.
to determine the safety and robustness of the technology
.
”

While it's impossible to estimate how much MASTER therapy might cost when it is eventually approved for clinical use, Brudno is optimistic that MASTER therapy will be significantly cheaper than existing CAR-T regimens
.

Original text retrieval

Agarwalla, P.
, Ogunnaike, EA, Ahn, S.
et al.
Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells.
Nat Biotechnol (2022).
https://doi.
org/10.
1038/s41587- 022-01245-x