T cell therapy is an innovative option to fight cancer tumors. However, before patients can receive treatment, they must first destroy the original immune system in the body through chemotherapy or radiation therapy. The potential for new functions of proliferating T cells may change in the future.
Synthetic receptor helps T cells outperform existing immune system and fight cancer more effectively
In the latest study in “Nature”, a team of researchers from the University of California, Los Angeles (UCLA), Stanford University, and the University of Pennsylvania describe a T cell engineered with a synthetic interleukin-9 (IL-9) receptor that can be used in different It can complete the work under the condition of chemotherapy or radiotherapy, and has a significant anti-tumor effect on tumors in mice.
The synthetic IL-9 receptor engineered T cells were designed in the laboratory of Dr. Christopher Garcia at Stanford University. The team found that signaling through the synthetic receptor appears to confer new functions on T cells, and in the case of the synthetic IL-9 receptor, not only helps the engineered T cells defeat the existing immune system, but also kills cancer more efficiently cell.
In view of the common side effects after chemotherapy and radiotherapy, the research team believes that with this technology, it may be possible to re-evaluate the necessity of using chemotherapy and radiotherapy to clear the immune system before T cell therapy in the future. “This discovery is like opening the door for us to deliver T cells like a blood transfusion,” said study author Antoni Ribas, a senior research fellow at UCLA.
Synthetic IL-9 receptor gives T cells mixed properties
The new research stems largely from a paper by Ribas and Garcia in 2018, in which the two focused on the concept of how to use a synthetic version of IL-2 to stimulate the synthesis of transgenic-matched IL-2 receptors. body T cells. With this system, even after injecting T cells into a patient, medical teams can manipulate T cells through synthetic cytokines for treatment without affecting other cells in the body.
Inspired by this 2018 study, Anusha Kalbasi, MD, UCLA, and colleagues were also interested in testing other versions of the synthetic receptor, focusing on other cytokine signals that also come from the common gamma chain : on IL-4, IL-7, IL-9 and IL-21.
The team quickly noticed the peculiarities of IL-9. Unlike other cytokines that share gamma chains, IL-9 signaling is not active in native T cells, while synthetic IL-9 signaling gives T cells a combination of stem and killer cell properties, Kalbasi points out Significantly more powerful against tumors. In one of the cancer models, synthetic IL-9 receptor T cells even managed to cure more than half of the treated mice.
According to the research team, this therapy has shown its full potential in multiple systems.In mouse models of pancreatic cancer and melanoma, two difficult-to-treat cancers, the team used natural T-cell receptors orChimeric Antigen Receptor (CAR) T cellsTo target cancer cells, either injecting cytokines into mice or directly into tumors has shown success, and as research continues, it may be possible to overcome barriers in solid tumor treatment in the future.
References:
1.Nature, 2022, https://www.nature.com/articles/s41586-022-04801
2.https://www.uclahealth.org/news/ucla-study-identifies-receptor-could-alleviate-need-chemo
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