A few days ago, Shanghai Institute of Materia Medica, Chinese Academy of Sciences Yaping Li’s group published an online publication of engineered T lymphocyte membrane-decorated epigenetic nanoinducer of inteferons for cancer immunotherapy in the top international journal Nature Nanotechnology ( IFN) The latest research results of epigenetic nanoinducers to improve tumor immunotherapy.
The team creatively designed and constructed a "precise delivery + intelligent drug release integration" bionic nanovesicles, revealing the mechanism of action of the nano drug delivery system, and achieved tumor-specific IFN induction and at the same time overcoming immune tolerance Major breakthrough.
Hao Xishan, an academician of the Chinese Academy of Engineering and an expert on therapeutics of tumors, commented that this work is the first to combine epigenetic drugs with bionic nanotechnology and immunotherapy to achieve the targeted delivery of epigenetic drugs and immune checkpoint blocking effects. Successfully solved the two key problems of poor specificity and dual effects of epigenetic therapy. It is a major progress in the effective combination of epigenetic therapy and immunotherapy to treat tumors. Chinese Academy of Sciences academician, nanomedicine expert Zhao Yuliang evaluated that this work is a new milestone in the use of nano-drug delivery systems to improve the effectiveness and safety of cancer immunotherapy.
Let nanomedicine "put on" the camouflage "coat"
Combine inside and outside to "kill" the tumor
Traditional cancer treatment methods mainly include surgery, radiotherapy and chemotherapy. Although radiotherapy and chemotherapy are fast and effective, they often "kill a thousand enemies and damage themselves 800", causing a series of toxic side effects such as bone marrow suppression, hair loss, and skin ulcers, causing cancer patients to suffer from the pain.
In recent years, the emergence of immunotherapy has brought hope to cancer patients.The main reason why cancer cells are rampant in the human body is that they can use a variety of methods to escape the "hunting and killing" of the human immune system. One of the strategies is to grow an immunosuppressive protein (PDL1 protein) on the surface of cancer cells to bind its counterpart protein (PD1 protein) on T cells (an immune cell that can kill diseased cells), making T cells "sleepy" "And lose the ability to kill cancer cells. Immunotherapy can "awaken" the human body's immune response and then kill cancer cells. This is a major breakthrough in the field of cancer treatment in recent years.
However, immunotherapy often activates immune cells in other parts of the body uncontrollably, and then attacks normal tissues, causing serious side effects. Therefore, how to accurately control immune activation in cancer tissues and effectively overcome immune tolerance is the key to achieving safe and effective cancer immunotherapy.
Researcher Li Yaping's team from Shanghai Institute of Materia Medica, Chinese Academy of Sciences has constructed a new bionic immunomodulatory drug delivery system. They packaged the drug ORY-1001 into the highly expressed T cell membrane vesicles of PD1 , and constructed a new type of immunomodulation Agent (referred to as OPEN).
In layman's terms, it is to "put on" the T cell membrane "coat" with high expression of PD1 for nanomedicine, and use it to actively identify PDL1 on the surface of cancer cells and use it to enter the cancer cells, then take off the camouflage and release ORY-1001 up-regulates the secretion of IFN , allowing cancer cells to express more antigen-presenting molecules MHC-I and PDL1. MHC-I allows cancer cells to expose themselves more and increase the possibility of being recognized by T cells, while PDL1 up-regulates It will actively recognize the PD1 of OPEN, leading to more OPENs entering the cancer cells. In this way, the intracellular OPENs and T cells “combine inside and outside”, constantly recruiting more T cells and OPENs, forming a virtuous circle, and finally killing the tumor.
This achievement presents three highlights:
precise killing, activating immunity, and maximizing strengths and circumventing weaknesses
Li Yaping's research team explained,Many immunotherapies activate immune cells in other parts of the human body at the same time when treating cancer, and then attack normal tissues in a way that "six relatives do not recognize", causing side effects. "How to precisely activate the immune cells at the tumor site without affecting the immune cell activity in other parts of the body is our current focus."
The "coat" of PD1's immune cell membrane, disguised as immune cells, will not "actively attack" normal tissue cells in the body, and when OPEN encounters cancer cells, the cancer cells will mistake them for immune cells, so it stretches Out of PDL1, actively identify and “catch” them. In this way, OPEN is “swallowed” into cancer cells, and then plays a role in killing cancer cells, making immune regulation targeted, realizing the transformation of “universal” into “specialty” and overcoming them. Side effects of immune regulation.
In addition, in the field of immunotherapy, cancer tissues are divided into "hot" and "cold". Here, cold and heat respectively represent more and less immune cells in the tumor. If there are many immune cells around the cancer cell, it is easily regulated by immunomodulators, and the immune cells will spontaneously kill the cancer cells. On the contrary, if the immune cells are lacking, the response rate of the cancer cells to immunotherapy will be greatly reduced. After OPEN enters the cancer cells, by releasing ORY-1001, the characteristics of the cancer cells are changed, allowing the cancer cells to secrete more IFN and up-regulating the expression of MHC-I, making the cancer cells easier to be "monitored" by the human immune cells. In turn, more immune cells are recruited, so that "cold" becomes "hot". This successfully activates the immune system and improves the responsiveness of cancer immunotherapy.
Turning "enemy" into "friend" and optimizing strengths and avoiding weaknesses are also one of the important highlights of this achievement.
For immunotherapy, the immune tolerance produced by cancer tissue is a headache. Once the human body's immune cells receive the immunosuppressive signal, they will lose their combat effectiveness and be obediently "withdrawal".
"The clever thing that OPEN puts on the "coat" of highly expressing PD1 immune cells is that OPEN wearing this "coat" will recognize the PDL1 protruding from cancer cells through PD1, and block the side effects caused by the upregulation of PDL1."Li Yaping researcher team said.
In addition, OPEN itself can also be swallowed into cancer cells through the combination of PD1/PDL1, further exerting immune regulation. So far, OPEN has successfully used its own up-regulated PDL1 expression in cancer cells and cleverly The shortcomings are turned into advantages, and the “enemy” is turned into “friends”, and the anti-cancer effect can be fully exerted.
Although there are still many problems with the anti-cancer strategy of immunotherapy, with the development of life science and material science, more and more Many precision drug delivery systems have been developed and targeted to solve the problems of immunotherapy. "We can believe that in the near future, the bionic immune regulation drug delivery system will play a more important role in the field of anti-cancer. The majority of cancer patients bring good news. "Researcher Li Yaping said.
Chief Editor Deng Qingyuan
Source Pudong released
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