Cancer has always been called an incurable disease, but in fact, medical and scientific research have never stopped conquering cancer. With the continuous advancement of scientific research, there are many ways for humans to deal with cancer, including chemotherapy, radiation therapy, immunotherapy, targeted therapy and other treatment methods, which greatly improve the remission rate and survival time of cancer patients. However, it is still difficult to completely eliminate cancer cells with current technology.
A research literature recently published in Frontiers in Oncology, researchers from Yale and Home Rhode Island have combined targeted therapy and immunotherapy to achieve efficient tumor elimination in animal trials. The researchers pointed out that this technology may make it possible to completely cure advanced cancers and can also prevent recurrence. How are these technologies implemented? Today, let’s share with you the new technology that is expected to become a “curable” of cancer.
Many friends know that cancer is a malignant disease in human cells, and the mutated cells have abnormal proliferation, involving normal cells and tissues and organs, which ultimately leads to serious damage to the patient's function, and even a fatal malignant disease. The reason why cancer treatment is difficult is precisely because of this. Some treatment methods can kill cancer cells, but at the same time it can damage normal cells in the human body, causing an embarrassing situation of "injuring one thousand enemies and hurting eight hundred by one"; some therapies can not destroy their own cells, but their effect on cancer cells is also relatively weak, and it is difficult to play a good therapeutic role.
If there is a method that can accurately locate cancer cells, deliver drugs to cancer cells to play a role, kill cancerous cells without affecting the health of normal cells, this therapy is ideal; and playing the powerful role of the human body's autoimmune system and killing abnormally proliferating cancer cells through immune cells is also another direction for cancer treatment. This new research is a "new weapon" that combines two powerful tools of targeted therapy and immunotherapy for .
This recently published new study uses a targeted technology of low pH insertion peptide (pHLIP) and combines it with the interferon gene stimulating factor (STING) activator that has been researched in recent years to achieve the combination of targeted therapy and immunotherapy, achieving good anti-cancer effects. What are the two new technologies and how they combine and play a magical role? Let’s continue to talk about it below.
low pH insertion peptide technology
low pH insertion peptide (pHLIP) technology is actually not a brand new technology. The research on this targeting technology has been started since the 1990s and has been developing and progressing. "wild type" pHLIP was originally derived from the C-helix of bacterial rhodopsin, containing the polar end and a central transmembrane domain, containing two aspartic acid residues, conferring its pH-dependent activity.
low pH insertion peptides show three different states in the human body: status Ⅰ—— pHLIPs are basically non-structural soluble monomers or low-order multimers in aqueous solution. status II - In the presence of the membrane, pHLIPs remain essentially structureless under neutral and alkaline, and reversibly bind to the outer blades of the membrane in the form of a monomer. status III - Under acidic conditions (pH ~ 6 or below), pHLIPs form stable monomer transmembrane α spirochetes, and their C-terminus is inserted into the lumen of liposome or the cytoplasm of cells.
At normal physiological pH value ~7.4, pHLIPs exist in states I and state II, interact with the external surface of the cell, but exchange with the water environment. Due to the effects of hypoxia, ischemia, or abnormal metabolic processes, many pathological conditions can produce a more acidic extracellular environment. An important example of this acidity is in solid tumor . Due to its enhanced metabolic activity, blood supply is damaged, membrane-bound carbonic anhydrase activity is reduced, and coupled with the Worburg effect, cancerous tumors produce an acidic extracellular environment with a pH of about 6.This pH is low enough to protonate the aspartic acid residues in the transmembrane domain of the pHLIPs, inserting the pHLIPs into the cells, where they are relatively stable and thus accumulate in acid tumor cells.
Therefore, the insertion of peptides at low pH will not affect the pH based on neutral normal cells, but it has good selectivity and penetration effects for tumor cells with acidic outer membranes, and can play a good targeting role in the diagnosis and treatment of cancer.
interferon stimulating factor agonist (STINGa)
interferon stimulating factor (STING) is a key signal transduction molecule involved in the human immune response. It can be started by DNA of pathogens and host cells, thereby inducing the secretion of interferon and pro-inflammatory cell molecules, thereby achieving an important role in resisting viral infections and intracellular bacterial infections. In addition to preventing infection, interferon stimulating factor also has the effect of regulating spontaneous anti-tumor immune responses in the body. That is to say, interferon stimulating factor is a very important immune factor for identifying and killing tumor cells.
In recent years, research on interferon stimulating factor agonists has been underway. Through this activator to effectively activate STING, the activation of the autoimmune system in fighting cancer cells can be achieved, and cancer control can be strengthened through the role of the immune system, which is safe and efficient.
In recent years, the research on STING agonists has made breakthrough progress, but it is still facing huge challenges to achieve efficient clinical application. This agonist may develop resistance, and the sensitivity of different mutations to drugs is also different. At the same time, it may also cause an uncontrollable inflammation storm , which will affect health. How to reduce the immunotoxicity of STING agonists, etc., still need to be further solved.
In the new study published this time, scientists reacted with a low-pH insertion peptide and a STING agonist to form an interpolymer. After this drug enters the blood, under the action of a low-pH insertion peptide, if this drug encounters normal cells with neutral pH, the drug will only pass by without any impact. If it encounters acidic cancer cells, the low-pH insertion peptide will play its targeting role, and will penetrate the cell membrane and enter the cancer cells. At this time, the link between the two drugs will be broken and a "self-immolation" effect will occur. The STING agonist will further activate the activity of immune cells, thereby killing tumor cells.
The interpolymer produced through this technology is like an missile installed with a precise guidance system. The low pH insertion peptide is a guidance system for accurately positioning cancer cells, while STING agonists are the "ammunition" that plays the role of destroying cancer cells. The combination of the two has achieved twice the result with half the effort.
In this study, scientists conducted drug tests with mice with colon tumor . This interpolymer was injected into 20 tumor model mice. After one injection, 18 of the tumors completely disappeared within a few days. In the tumor model mice in the placebo group, only STING agonists were used. Although the tumor growth slowed down, the tumor still existed, and there was a significant difference between the two groups.
. The researchers also injected tumor cells again into mice whose tumors disappeared, but the results showed that although the tumors had been eliminated, the tumor did not appear again within 60 days. The researchers believe that this indicates that immune memory has been formed, that is, this interpolymer can not only kill cancer cells, but also play a role in preventing cancer cell recurrence. Trials like
are currently based on data from animal models, but good efficacy gives us endless hope. We have reason to believe that the combination of targeted technology and immunotherapy can provide a safe and effective treatment method to remove cancer cells. For the treatment of multiple solid tumor cancers, it is expected to provide a new and efficient treatment method, and will play an immune effect in preventing cancer recurrence to a certain extent.
hopes that such new technologies can become more and more mature and be applied to clinical practice as soon as possible, benefiting more cancer patients!
