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Comments | Zhao Yuliang (Academician of the Chinese Academy of Sciences), Hao Xishan (Academician of the Chinese Academy of Engineering) Immunotherapy is a revolutionary advancement in the field of tumor treatment.
The level of type I interferon (IFN) in tumors is related to colon cancer, melanoma, and triple negative breast cancer.
The prognosis of a variety of tumors is closely related
.
Although recombinant human IFN can be injected clinically to increase its intratumoral level, its tumor targeting is poor, the curative effect is low, and it is prone to obvious systemic immune toxicity
.
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.
In particular, the up-regulation of intratumoral IFN will inevitably induce a variety of The expression of immune checkpoint molecules promotes tumor immune escape and thus immune tolerance
.
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
.
On September 27, 2021, the researcher of Shanghai Institute of Materia Medica, Chinese Academy of Sciences (hereinafter referred to as Shanghai Institute of Materia Medica) researcher Li Yaping's group published an article T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy on Nature Nanotechnology
.
This research creatively constructed a bionic nanovesicle with "precise delivery + intelligent drug release integration", revealed the mechanism of action of the nano drug delivery system, and achieved tumor-specific interferon induction and at the same time overcoming immune tolerance.
An important breakthrough
.
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)
.
Figure: A.
Construction of PD1 overexpressing CTLL-2 cells and preparation of ORY-1001 nanovesicles (OPEN)
.
B.
OPEN is recognized by tumor cells PDL1 and incorporated into cells, up-regulates IFN expression, increases T cell infiltration in the tumor microenvironment and promotes cytotoxic T cell (CTL) activation, while blocking PDL1 mediated immune escape
.
C.
OPEN specifically targets tumors, significantly up-regulates IFN expression in tumors, promotes antigen presentation, improves cytotoxic T cell infiltration in tumors and effectively relieves immunosuppression caused by ORY-1001
.
D.
OPEN significantly inhibits the growth of breast cancer and melanoma
.
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.
It aims to improve the anti-cancer activity and promote immune escape including IFN.
The curative effect of active molecules and the reduction of immune side effects provide new ideas
.
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
.
Expert comment Zhao Yuliang (Academician of the Chinese Academy of Sciences, Director of the National Nanoscience Center) This research result is the first report that the Nano Drug Delivery System (NDDS) carries epigenetic drugs and combines with immunotherapy to overcome immune tolerance and improve epigenetics The specificity of regulation and the effect of immunotherapy have remarkable originality and uniqueness
.
"Successfully solved the two-sided problem of epigenetic drugs.
It is a new milestone in the use of NDDS to improve the efficacy and safety of cancer immunotherapy
.
" Expert comment Hao Xishan (academician of the Chinese Academy of Engineering) It is combined with immunotherapy to achieve the tumor-targeted delivery of epigenetic drugs and the blocking effect of immune checkpoints, and successfully solves the two key problems of poor specificity and dual effects of epigenetic therapy, which is epigenetic A major advancement in the effective combination of therapy and immunotherapy to treat tumors
.
Original link: https://doi.
org/10.
1038/s41565-021-00972-7 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights , The offender must be investigated
.
The level of type I interferon (IFN) in tumors is related to colon cancer, melanoma, and triple negative breast cancer.
The prognosis of a variety of tumors is closely related
.
Although recombinant human IFN can be injected clinically to increase its intratumoral level, its tumor targeting is poor, the curative effect is low, and it is prone to obvious systemic immune toxicity
.
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.
In particular, the up-regulation of intratumoral IFN will inevitably induce a variety of The expression of immune checkpoint molecules promotes tumor immune escape and thus immune tolerance
.
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
.
On September 27, 2021, the researcher of Shanghai Institute of Materia Medica, Chinese Academy of Sciences (hereinafter referred to as Shanghai Institute of Materia Medica) researcher Li Yaping's group published an article T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy on Nature Nanotechnology
.
This research creatively constructed a bionic nanovesicle with "precise delivery + intelligent drug release integration", revealed the mechanism of action of the nano drug delivery system, and achieved tumor-specific interferon induction and at the same time overcoming immune tolerance.
An important breakthrough
.
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)
.
Figure: A.
Construction of PD1 overexpressing CTLL-2 cells and preparation of ORY-1001 nanovesicles (OPEN)
.
B.
OPEN is recognized by tumor cells PDL1 and incorporated into cells, up-regulates IFN expression, increases T cell infiltration in the tumor microenvironment and promotes cytotoxic T cell (CTL) activation, while blocking PDL1 mediated immune escape
.
C.
OPEN specifically targets tumors, significantly up-regulates IFN expression in tumors, promotes antigen presentation, improves cytotoxic T cell infiltration in tumors and effectively relieves immunosuppression caused by ORY-1001
.
D.
OPEN significantly inhibits the growth of breast cancer and melanoma
.
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.
It aims to improve the anti-cancer activity and promote immune escape including IFN.
The curative effect of active molecules and the reduction of immune side effects provide new ideas
.
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
.
Expert comment Zhao Yuliang (Academician of the Chinese Academy of Sciences, Director of the National Nanoscience Center) This research result is the first report that the Nano Drug Delivery System (NDDS) carries epigenetic drugs and combines with immunotherapy to overcome immune tolerance and improve epigenetics The specificity of regulation and the effect of immunotherapy have remarkable originality and uniqueness
.
"Successfully solved the two-sided problem of epigenetic drugs.
It is a new milestone in the use of NDDS to improve the efficacy and safety of cancer immunotherapy
.
" Expert comment Hao Xishan (academician of the Chinese Academy of Engineering) It is combined with immunotherapy to achieve the tumor-targeted delivery of epigenetic drugs and the blocking effect of immune checkpoints, and successfully solves the two key problems of poor specificity and dual effects of epigenetic therapy, which is epigenetic A major advancement in the effective combination of therapy and immunotherapy to treat tumors
.
Original link: https://doi.
org/10.
1038/s41565-021-00972-7 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights , The offender must be investigated
.
