Nat Nanotech: A major breakthrough in tumor immunotherapy, Li Yaping of Shanghai Institute of Medicine developed epigenetic regulation nanovesicles to improve tumor immunotherapy

Immunotherapy is a revolutionary development in the field of tumor treatment.
The level of type I interferon (IFN) in tumors is closely related to the prognosis of many tumors including colon cancer, melanoma, and triple-negative breast cancer
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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
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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
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On September 27, 2021, Li Yaping's research group at Shanghai Institute of Materia Medica, Chinese Academy of Sciences published a research paper titled: T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy in the journal Nature Nanotechnology
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The study improved tumor immunotherapy by engineering T lymphocyte membrane modified interferon epigenetic nanoinducers, and creatively constructed a "precise delivery + intelligent drug release integration" bionic nanovesicles, revealing the nano drug delivery The mechanism of action of the system has achieved a major breakthrough in inducing tumor-specific interferon and simultaneously overcoming immune tolerance
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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 (PD-1) through genetic engineering technology, and obtained the cell membrane vesicles of the engineered cells; Then they wrapped albumin nanoparticles loaded with lysine-specific histone demethylase 1 (LSD1) inhibitor ORY-1001; finally, they surface-modified them with reduction-sensitive penetrating peptide M70 to obtain The epigenetic regulation of nanovesicles (OPEN)
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Figure: A.
Construction of PD1 overexpressing CTLL-2 cells and preparation of ORY-1001 nanovesicles (OPEN)
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Researchers found that after intravenous injection, OPEN can specifically target tumors, efficiently induce intratumoral IFN secretion, up-regulate the expression of tumor cells PD-L1 and major histocompatibility complex-I (MHC-I), and Further promote the uptake of OPEN, produce self-enhancing effect, increase cytotoxic T cell infiltration in tumors by 29 times, significantly reduce the immune side effects of ORY-1001, and effectively inhibit triple-negative breast cancer, melanoma or colon cancer in animal models Grow
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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
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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
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Academician Comments

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.
The effect of specificity and immunotherapy has remarkable originality and uniqueness
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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.

Original source:

Zhai, Y.