CAR-T is an effective method for the treatment of hematological tumors, but the price of CAR-T therapy is really daunting. For example, the domestically approved akirenza injection, the price of one injection is as high as 1.2 million. In addition, CAR-T cells need to be prepared using the patient’s own T cells, and the preparation process takes a lot of time. Critically ill patients who have money may not be able to wait for their own life-saving drugs. However, recently, an invention by University of North Carolina Yevgeny Brudno and others may solve both of these problems with CAR-T. He made a special gel MASTER, which only needs to mix the patient’s T cells and the engineered virus onto the gel to complete the preparation of CAR-T, and then the gel loaded with CAR-T cells can be directly implanted [1]. With this method,the preparation process of CAR-T can be shortened to less than 1 day, or even completed in a few hours. Costs will also drop significantly. In mice, CAR-T prepared using MASTER gel can effectively kill cancer cells throughout the body, even better than CAR-T prepared by traditional methods. 
MASTER gel implanted in vivo to release CAR-T cells With the approval and listing in China, CAR-T therapy has really caught fire for several waves on the Internet. In addition to the miraculous efficacy, the high price of CAR-T therapy has also become a hot topic of discussion. But let’s be honest, there’s a reason why CAR-T therapies are so expensive. In order to avoid rejection, current CAR-T cells need to be prepared from the patient’s own T cells. Doctors must first isolate the patient’s T cells from the blood and send them to a sterile laboratory for cultivation, modification and activation. The entire preparation process takes two weeks or more, and requires professional technicians to operate. In the United States, where labor costs are high, the cost of preparing a single CAR-T can be as high as $500,000. For patients, even if they can afford the cost of CAR-T treatment, they may not wait for the preparation to be completed. For example, in the clinical trial of CAR-T therapy axi-cel, 3 out of 111 patients died before CAR-T preparation was completed, and 4 patients had adverse events while waiting for CAR-T preparation and could not receive CAR-T injection< /span>[2]. 
Conventional method (left) and using MASTER (right) to prepare /span>In order to solve these problems of CAR-T, Brudno et al. developed a CAR-T preparation gel MASTER. The skeleton of MASTER is constructed of alginate and loaded with T cell activating factors such as CD3 antibody and CD28 antibody. When in use, it is only necessary to mix the T cells isolated from the patient’s blood with the engineered virus and drop it on the MASTER to complete the preparation of CAR-T. Moreover, MASTER gel has good biocompatibility and can be degraded in vivo. After the CAR-T preparation is completed, the MASTER gel together with the CAR-T cells in it can be directly implanted into the patient to release the CAR-T cells. In order to verify the therapeutic effect of CAR-T cells prepared by the MASTER method, the researchers conducted experiments with lymphoma mice. In the test, both MASTER and CAR-T cells prepared by traditional methods controlled the tumor within 45 days, and showed no obvious side effects. But at 100 days, mice in the MASTER group still had a 50 percent tumor-free survival rate, compared with 16.6 percent in the conventional group. 
Untreated mice (green), mice treated with conventional CAR-T (red) and treated with MASTER Tumor-Free Survival Curves of Mice
And, if re-inoculated with tumor cells on day 29 after treatment, MASTER-prepared CAR-T cells Still able to effectively inhibit the tumor, no tumor growth within 30 days. The mice in the conventional group, on the other hand, had significant tumor growth within two weeks of being re-inoculated with cancer cells. ResearchThe researchers believe that the CAR-T cells prepared by the MASTER method have better curative effect, which may be because the T cells do not need to be expanded in vitro during the preparation process, so that there are more memory cells in the prepared CAR-T cells. In addition, MASTER gel also plays a slow-release role. The paper’s author Brudno said: “MASTER technology is very promising in hematological tumors such as lymphoma, but we also expect to see how MASTER performs in solid tumors. We are working with Industry partners are collaborating to commercialize the technology, but there is still a lot of work to be done before clinical application.”And, although it is not yet possible to estimate the post-approval price of MASTER That’s how much, but Brudno is optimistic that it will be a lot cheaper than existing CAR-T therapies.
References:[1]. Agarwalla P, Ogunnaike E A, Ahn S, et al . Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells[J]. Nature Biotechnology, 2022: 1-9.[2]. Neelapu S S, Locke F L, Bartlett NL, et al. al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma[J]. New England Journal of Medicine, 2017, 377(26): 2531-2544.