Cheaper and faster
The main disadvantage of CAR-T therapy is the high price associated with the fact that the production process is complex, time-consuming and must be adapted individually to each patient. To solve this problem, researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed a Multifunctional Alginate Scaffolds for T cell Engineering and Release (MASTER) bioimplant, which both produces and releases CAR-T cells inside the body.
According to the existing CAR-T protocol, cells for immunotherapy are prepared within a few weeks using expensive and cumbersome processes. Clinicians first isolate patients' T cells and transport them to a manufacturing facility. At this facility, T cells are "activated" with antibodies for several days, preparing them for reprogramming. The researchers then use viral vectors to insert a chimeric antigen receptor gene into T cells, turning them into CAR-T cells targeted at cancer cells. Next, factors stimulating proliferation are introduced, and the number of CAR-T cells is increased. Finally, after these manipulations are completed, the cells are returned to the hospital and injected into the patient's bloodstream.
MASTER allows you to perform some of the steps in the patient's body. This is a biocompatible sponge material, on the surface of which a mixture of T cells from the patient and CAR carrier viruses is placed. The cells impregnate the MASTER and meet with pre-introduced antibodies and interleukins, which activate the cells and promote their proliferation. Almost immediately, the "semi-finished product" is ready for implantation.
The researchers implanted MASTER into mice with lymphoma. Inside the body, the CAR-T cell production process continues. First, T cells are activated by antibodies, and then interact with vectors that reprogram them into CAR-T cells. Next, interleukins enter, stimulating cell proliferation.
The group of mice that received MASTER was compared with mice that received ready-made CAR-T intravenously and a control group that received unmodified T cells.
It took at least two weeks to create CAR-T cells using standard technology, while the MASTER was ready for implantation just a few hours after taking the T cells. Minimal intervention creates healthier cells, and they show fewer markers associated with weak antitumor activity. In particular, the MASTER method leads to the creation of less differentiated cells, which leads to better resistance and greater antitumor activity. In addition, the cells show fewer markers of T-cell depletion.
Mice treated with CAR-T cells with MASTER were much better at fighting tumors and less likely to relapse than mice treated with conventional CAR-T cells.
The cost of immunotherapy using MASTER technology is difficult to estimate, but it can already be assumed that it will be significantly cheaper than existing treatment options with CAR-T cells.
The article by P.Agarwalla et al. Bioinstructive Implantable Scaffolds for Rapid In Vivo Manufacture and Release of CAR-T Cells is published in Nature Biotechnology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on North Carolina State University: In Animal Study, Implant Churns Out CAR-T Cells to Combat Cancer.