Immune treatment for tumors based on cholesterol metabolism regulation.

On July 29, Beijing time, Cell published the results of the collaboration between Xu Wei, a researcher at the Center for Molecular Cell Science Excellence and Innovation of the Chinese Academy of Sciences, Huang Chaolan, a professor of medicine at Peking University, and AWh Wheenfu, a professor at the University of California, San Diego.
the study developed a new method of CAR-T cell therapy based on the basic research of T-cell signal transduction.
T cells are natural anti-tumor warriors in the human body, relying on T-cell receptors (TCRs) to identify tumor antigens.
but not all TCRrs are targeted at tumor antigens, so people use genetic engineering techniques to install T cells with specific ally-identification tumor antigens of the chimeric antigen receptor (Chimeric antigen, CAR), the modified T-cells can accurately "kill" tumor cells in the body.
but CAR-T cell therapy also has obvious drawbacks.
CAR-T cells are too "active" to cause cytokine storms, causing risks, CAR-T cells in the body is not high in persistence, can not long-term monitoring of tumor cells, will lead to tumor recurrence.
Xu Wei's team is committed to the functional regulation of T cells, early discovery of TCR, PD-1 and other key receptors of the signal regulation mechanism and the development of cholesterol metabolism-based regulation of tumor immunotherapy.
the latest study, the researchers used immunology, mass spectrometry, biochemistry, biophysics and other technical means to study the signal transduction mechanism of the key signal molecule CD3, and found that CD3 can recruit the inhibitory signal molecule Csk through its ITAM signal base sequence, and through its BRS signal base sequence to recruit the activated signal molecule PI3K.
the integration of CD3 in the 28Z CAR currently used in the clinic reduces cytokine secretion and promotes cell growth and survival, improving overall sustainability.
in mouse models, the "upgraded" E28Z CAR-T antitumor activity increased significantly compared to the "original".
CAR-T cells loaded with CD3 - t, like an upgraded forklift fitted with a new engine, have longer life (better cell growth continuity) than the original forklift (28Z CAR-T cells), lower emissions (less cytokine secretion), and stronger tumor removal activity.
is currently in the experimental phase of the study in mice, and given the promising application of his treatment of hematomas and solid tumors, scientists will continue to explore ways to apply the results to clinical practice at an early date.
, Ph.D. students Wu Wei, Zhou Qiuping and Shi Xiaoshan, Ph.D. takeya Masubuchi, University of California, San Diego, co-author of the paper; Xu Wei, Huang Chaolan and Wei Enfu are co-authors of the paper; and Shanghai University of Science and Technology Professor WangPeng and Sun Jie of Zhejiang University participated in the study.
research work is supported by the Chinese Academy of Sciences, the National Natural Science Foundation of China, the Ministry of Science and Technology and the Ministry of Education.
Source: Center for Excellence in Molecular Cell Science.