Expensive CAR-T cell therapy difficult to load? Biological scaffolds can be implanted or new hope can be seen

American researchers have developed an implantable biological scaffold capable of producing and releasing highly efficient CAR-T cells. A proof-of-concept study of lymphoma in mice found that implant treatment was more effective than traditional CAR-T cell therapy.

T cells are part of the immune system and are able to recognize and destroy cells in the body that have been infected with invading pathogens. Chimeric Antigen Receptor T-cell (CAR-T) is an engineered T cell that can specifically target the clearance of tumor cells, thereby achieving the purpose of precise cancer treatment. CAR-T cell therapy shows good therapeutic effects in the clinical treatment of tumors, especially lymphoma. The main disadvantage of this cell therapy is that it is expensive, because it needs to be customized for each patient and the manufacturing process is complex and time-consuming, with a price of up to hundreds of thousands of dollars per dose.

Fig. 1 CAR-T mechanism of action (Source: [1])

To address this conundrum, researchers from north Carolina State University and the University of North Carolina in conjunction with the Department of Biomedical Engineering developed a biotechnology, multifunctional Alginate Scaffolds for T-cell Engineering and Release (MASTER), which was validated in a proof-of-concept study on mouse lymphoma. Studies have found that MASTER is able to produce and release highly efficient CAR-T cells, and the therapeutic effect is better than traditional treatment. The findings were published in Nature Biotechnology.

Figure 2 Research results (Source: Nature Biotechnology)

The researchers first isolated T cells from patients and then "activated" T cells with antibodies for several days in preparation for reprogramming. Once the T cells were activated, the researchers used the virus to introduce the CAR gene, reprogramming the T cells into CAR-T cells, and then further stimulating car-T cell proliferation, expanding them to the desired number.

MASTER is a biocompatible spongy material that facilitates the programming of cellular genes. In addition, the MASTER is also saturated with interleukins, which can promote cell growth. The researchers poured programmed CAR-T cells on the MASTER, which in turn was decorated with antibodies that activated the T cells, so the cell activation process began almost immediately. At the same time, the MASTER is surgically implanted into the patient's body.

Figure 2 Master promotes activation and retroviral mediation of primitive human T cells (Source: [3])

Subsequently, the researchers conducted further validation in a conceptual study of mouse lymphoma: one group received MASTER CAR-T cell therapy, and the second group was treated with CAR-T cells made using traditional methods and injected intravenously. Both groups were compared to a control group that received nonprogrammed T cells. The final findings show that mice treated with CAR-T cells by MASTER are far superior to mice that receive traditional CAR-T cell therapy in terms of anti-tumor. In the long run, when mice face lymphoma recurrence, the anti-cancer effect is particularly obvious.

Figure 3 Conventional CAR-T cell therapy vs MASTER implantation therapy (Source: [3])

The researchers said that traditional CAR-T cell therapy takes at least two weeks to go from "raw" T cells to manufacturing CAR-T cells for clinical use, while MASTER technology places the tedious and time-consuming activation, reprogramming and expansion steps to produce CAR-T cells in patients, thereby turning the multi-week process into a single-day process, and the time taken to produce and release CAR-T cells is shorter. For patients with rapidly developing diseases, shortening the time is a more critical step.

Yevgeny Brudno, corresponding author of the study, said: "We are working with industry partners to commercialize MASTER technology. But before we can begin exploring the safety of clinical trials involving human patients, we need to do further work, for example, to establish the safety and robustness of this technology in animal models. Although it is currently impossible to estimate the cost of treatment for MASTER, if it can eventually be approved for clinical treatment, the cost will be significantly lower than the existing CAR-T treatment regimen. He also noted that master technology is very promising in terms of fluid tumors such as lymphoma, but they are particularly eager to see how MASTER manifests itself on solid tumors, such as pancreatic cancer and brain tumors.

Cancer treatment is not only a long and painful treatment process, but also expensive and unbearable, and the effective and relatively low cost can be said to solve the "urgent need" of patients, which is the path that medical research has been exploring. Stent-implantable cancer therapies fight cancer from another angle, with faster, more efficient therapies bringing the dawn of cure to cancer patients.

Source: Tianyancha, only for academic exchanges.

Written by | Qingyao

Typography | Muzijiu

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Resources:

[1]https://scrubbing.in/car-t-therapy-genetically-re-engineering-your-cells-to-target-cancer/

Zheng Nairong,Zhang Xiaoyan,Xu Jianqing. Research progress of CAR-T cell immunotherapy[J/OL].Fudan Journal (Medical Edition):1-6[2022-03-29].http://kns.cnki.net/kcms/detail/31.1885.R.20220224.1431.020.html

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