On September 27th, Li Yaping, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (hereinafter referred to as Shanghai Institute of Materia Medica), published in Nature Nanotechnology an engineered T lymphocyte membrane modified interferon (IFN) epigenetic nanoinducer to improve tumor immunotherapy.
Zhao Yuliang, academician of the Chinese Academy of Sciences and director of the National Center for Nanoscience, believes that the research results reported for the first time that the Nano Drug Delivery System (NDDS) carries epigenetic drugs and is combined with immunotherapy to overcome immune tolerance and improve epigenetic regulation.
Immunotherapy is a revolutionary development in the field of tumor treatment.
Although chemotherapy drugs, molecularly targeted drugs and epigenetic drugs can also induce IFN expression in tumors to a certain extent, the effects are not ideal due to poor specificity.
Therefore, how to selectively increase the level of immune molecules such as IFN in tumors, and at the same time overcome the immune tolerance induced by them, is a major scientific problem that needs to be solved urgently in the field of tumor immunotherapy
In response to the above-mentioned major clinical needs, the team of Shanghai Institute of Medicine Researchers Zhang Pengcheng and Li Yaping first constructed T cells with high expression of programmed death receptor-1 (PD1) through genetic engineering technology, and obtained the cell membrane vesicles of the engineered cells; The albumin nanoparticles loaded with the lysine-specific histone demethylase 1 (LSD1) inhibitor ORY-1001 were wrapped with them; finally, they surface-modified them with the reduction-sensitive penetrating peptide M70, and obtained the table Observed genetic regulation of nanovesicles (OPEN)
Researchers found that after intravenous injection, OPEN can specifically target tumors, efficiently induce intratumoral IFN secretion, up-regulate the expression of tumor cells PDL1 and major histocompatibility complex-I (MHC-I), and further promote OPEN intake produces self-enhancing effect, increases cytotoxic T cell infiltration in tumors by 29 times, significantly reduces the immune side effects of ORY-1001, and effectively inhibits the growth of triple-negative breast cancer, melanoma or colon cancer in animal models
This research opens up new directions for the "precise delivery + intelligent drug release integration" technology to regulate epigenetics, overcome immune tolerance, and improve tumor immunotherapy.
Academician Hao Xishan of the Chinese Academy of Engineering said that the study combines epigenetic drugs with bionic nanotechnology and immunotherapy for the first time, achieving tumor-targeted delivery of epigenetic drugs and immune checkpoint blocking effects, and successfully solved epigenetic therapy.
The doctoral student Zhai Yihui of Shanghai Institute of Materia Medica and the doctoral student Wang Jin of Renji Hospital of Shanghai Jiaotong University are the co-first authors of the paper, and Li Yaping and Zhang Pengcheng are the co-corresponding authors
Related paper information: https://doi.
https://doi.
org/10.
1038/s41565-021-00972-7 https://doi.
org/10.
1038/s41565-021-00972-7
This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only.
This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of
the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed
description of the concern or complaint, to
service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content
will be removed immediately.
