A wine ingredient can be used for controllable tumor immunotherapy

Photo courtesy of Ye Haifeng

In Chinese and Western cultures, wine symbolizes different meanings, but its inherent biologically active ingredient resveratrol (RES) is the same
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This achievement by the East China Normal University, College of Life Sciences, synthetic biology research center medical researcher Ye Haifeng team completed and published on August 17 in the United States , "National Academy of Sciences on the Academy of Sciences"
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Oriented to clinical issues

Chimeric antigen receptor T cell therapy (CAR-T therapy) transforms the patient’s own T cells to recognize tumor antigens, thereby eliminating tumor cells, fundamentally changing traditional cancer therapy.
CAR-T therapy is also considered to be One of the most promising therapies for humans to overcome cancer
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However, with the deepening of clinical research, the side effects of CAR-T therapy are unexpected
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The most powerful strategy to solve the cytokine storm is to control the activity of CAR-T cells, and how to safely and accurately control its activity is a common challenge faced by scientists all over the world
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"Controlling engineered T cells in the'function switch' mode can reduce the side effects of CAR-T therapy
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Therefore, Ye Haifeng’s team was guided by clinical issues and took resveratrol as a breakthrough.
Over 6 years, the team designed and constructed a transgene expression system regulated by resveratrol, and used resveratrol to regulate CAR in T cells.
Expression (ON) and inhibition (OFF) to achieve controllable CAR-T cell immunotherapy
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Provide new tools for precision medicine

Resveratrol is a non-flavonoid polyphenol compound that is beneficial to human health.
It is a safe natural small molecule that can be designed to switch gene expression regulation
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In order to achieve safer tumor immunotherapy through the functional off/on mode, the researchers constructed an inhibitory system and an induction system for resveratrol to regulate the expression of transgenes
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The first author of the thesis, Yang Linfeng (graduated), a 2016 doctoral student in the School of Life Sciences, East China Normal University, introduced that the team used resveratrol-responsive trans-activator and trans-repressor proteins to develop inhibition (RESrep) and induction (RESind), respectively.
Transgene expression control device
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After optimization, the device can control the expression of CAR of human T cells and the function of CAR-mediated anti-tumor immunotherapy
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Further studies have shown that the RESrep-CAR device can effectively inhibit T cell activation in primary T cell and xenograft tumor mouse models
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"In a mouse model of leukemia, oral or intraperitoneal injection of resveratrol can precisely regulate the killing of tumor cells by T cells expressing CAR receptors, thereby prolonging the survival time of mice
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So far, the research team has successfully constructed an inhibitory system and an induction system for resveratrol to regulate transgene expression, adding a powerful gene control tool to the research of synthetic biology
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In addition, the resveratrol-regulated gene expression system constructed by the institute can also be used to precisely regulate the delivery of therapeutic proteins encoded by any gene and other precise and controllable drug delivery, providing a safety for future precision medicine based on gene and cell therapy , Accurate and controllable new tools
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(Source: Qin Zhiwei, China Science News)

Related paper information: https://doi.
org/10.
1073/pnas.
2106612118