Author: Zhang Jia Xing Release Date: 2018-10-25
The 2018 Nobel Prize in Physiology or Medicine, not long ago, was presented to the findings of immunological checkpoints (PD-1 and CTLA-4). This is the second time that PD-1 has been spotlighted by a spotlight since former US President Carter announced that PD-1 immunotherapy has cured his melanoma.
It is very similar to the artist's star route. If the previous fire, PD-1 is still the "most potential" of the green, then this fire has become the "most powerful". Relevant information shows that the US FDA has approved 5 kinds of PD-1/PD-L1 antibody drugs approved by the beginning of this year, including the well-known "O drug" and "K drug", as well as Roche's Tecentrip, Pfizer and Merck. Bavencio and Imfinzi produced by AstraZeneca in the UK and Switzerland.
According to the financial report released by the pharmaceutical giant, the sales of “K medicine†increased from US$0.8 billion in the first quarter of 2015 to US$1.667 billion in the second quarter of 2018, and “O medicine†was US$0.7 billion in the first quarter of 2015. It grew to $1.627 billion in the second quarter of 2018. The therapeutic strength of PD-1 immunological checkpoint inhibitors is evident from the sales volume.
Against the tumor cells, humans seem to find the right path. How does the “immunization checkpoint inhibitorâ€, a new cancer control strategy, work? Can humans end the onset of cancer?
The immune checkpoint inhibits the "sheep skin" that tears off the tumor cells.
Two of the winners of the Nobel Prize in Physiology or Medicine were James Allison, a professor at the University of Texas-Anderson Cancer Center. He first discovered that blocking CTLA-4 can activate the immune system. T cells, to attack cancer cells, he also developed CTLA-4 antibody for immune tumor therapy for the first time; and Professor Ben Youyou, a professor at Kyoto University in Japan, who first discovered that PD-1 is an inducer of activated T lymphocytes, followed by Studies have revealed that PD-1 is a negative regulator of immune response.
Due to the success of the PD-1 antibody drug, the award-winning CTLA-4 appears to be somewhat obscure. In fact, the CTLA-4 antibody drug was approved by the US FDA as early as 2011, but only BMS has been approved for listing so far. Ipilimumab, a drug of Bristol-Myers Squibb, has not been approved for marketing due to poor clinical performance in other clinical trials.
What is the relationship between CTLA-4 and PD-1, the two letters that differ greatly? Why are you winning together?
"They are all immune checkpoints." Yang Guanghua, a special professor at Shanghai Ocean University and founder of Bion Bio, said that the term "immune" and "checkpoint" will be better understood. "Immunization" means that it exists in the immune response system. The "checkpoint" can be understood as the "checkpoint" established by the traffic police. The cells in the body will be inspected by the immune system, and the "black number" will be considered as "self-family" and released. If it is not recognized as a "bad", it will be activated as a "bad guy", and the body's immune response will be initiated. T lymphocytes will "siege" the cancer cells and destroy them.
It can be understood that PD-1 or CTLA-4 evolved to prevent lymphocytes from killing "self" and only "non-me". Because of this, many immunologists have identified the nature of immunity as the identification of “self†and “non-selfâ€.
The problem came, and the mechanism of the "checkpoint" was learned by the tumor cell "corps". "Tumor cells are a kind of very awkward cells, which will cause them to escape." Yang Guanghua said that in the contest with the immune system, after thousands of years of evolution, they put on "hypothetical sheepskin" to let themselves not be Identification.
The "sheep skin" that makes cancer cells appear hypocritical is called "ligand." For example, where the ligand of PD-1 is PDL-1, the PD-1 on the T cell is to check the cancer cells, and the cancer cells stick out the small hand of PDL-1, and repeatedly say "Friends of the Army", T cells are verified, Just glance at them and close your eyes.
Scientific studies have shown that PD-L1 (PD-1 ligand) is significantly increased in tumor tissue than normal tissues and is expressed on the surface of most tumor cells, including non-small cell lung cancer, melanoma, gastric cancer, colon cancer, breast cancer, Pancreatic cancer, kidney cancer, etc., while reducing the expression level of PD-1 can improve the overall survival rate of patients. That is to say, the tumor cells allow a large amount of protein on the surface of their cells to allow the "checkpoint" to scan without warning, showing a "friendly" appearance and paralyzing T cells. The listed antibody drug is to suppress the T cell's "checkpoint", so that it is not blinded by "friendly sheepskin", and then attack the tumor cells.
Anti-cancer road has turned 3 bends and interventions are more and more effective
"Now the incidence of tumors is getting higher and higher, and on the other hand, there are more and more opportunities for tumors to survive for a long time." Zhang Xuemin, a member of the Chinese Academy of Sciences and a cell biologist, said that with the deepening of cancer research, the intervention of cancer will More and more effective.
From radiotherapy and chemotherapy to targeted therapy to today's immunotherapy, it is based on changes in people's understanding of the mechanisms of tumorigenesis. "Most patients will ask themselves after illness, but also ask the doctor: Why do you get a tumor? This is also a question that scientific research has to answer." Zhang Xuemin explained that the stage of cancer treatment is roughly divided into three segments: very early, people realized The tumor grows very fast, which is a problem in the cell proliferation cycle. Therefore, the chemotherapeutic drug is based on the growth pathway that blocks the tumor cell cycle. Later, it is recognized that the tumor is a problem of gene mutation, so a targeted drug was invented, and the gene expression control was suppressed. Tumor cells, targeted drugs have a good effect, but still can not solve the tumor; later found that the tumor in the immune system can "escape", "walk away" and "invisible", the immune system can not identify them, people began to explore why it can not be identified ? It was found that an immune checkpoint represented by PD-1 blocked the T cell recognition pathway. Then, the scientists developed anti-inhibitory antibodies against it and later proved effective.
It can be seen from three different stages that people's perception of cancer has changed: from the initial focus on the tumor cells themselves, the treatment of tumors in isolation and isolation, to explore its "struggle" relationship with the human immune system, understanding The importance of association and environment, people's understanding of cancer is more systematic and in-depth.
"But even with immunotherapy, only about 20% of advanced patients have the opportunity to get a new life and get a long-term survival." Zhang Xuemin said, so the understanding of the tumor is deeper, with the scientific understanding of the tumor more and more In-depth, people will continue to discover new treatments to improve efficiency.
Accurate treatment still needs to be perfected in exploring anticancer drugs
As Zhang Xuemin said, 20% is the effective treatment of single-agents at the current immune checkpoints for the general population, so medical scholars are still doing a lot of work on improving the efficacy, such as combined immunotherapy.
Relevant data show that the dual immuno-blocking mode was approved by the FDA in 2011 and 2017 for malignant melanoma and renal cell carcinoma, respectively, which also indicates that double immuno-blocking has become an important model for clinically improving the efficacy of immunological checkpoints. .
Excitingly, CTLA-4 and PD-1 control immune cells do not overlap with the "combat" stage of tumor cells, and can be "two-pronged": CTLA-4 monoclonal antibody can block T cell inhibition signals and regulate T cells. The degree of activation promotes the further proliferation of T cells, which occurs mainly in lymph nodes and acts on the early stages of immune effects. PD-1 inhibitors block the inhibition of PD-1 in the interaction phase between T cells and antigen presenting cells, and promote the proliferation of activated T cells.
Chen Likun, a professor at the Affiliated Tumor Hospital of Sun Yat-sen University, said in his related research: "At the same time, the key points of these two steps are blocked at the same time, which may bring unexpected results."
"This year's "New England Journal" has published a number of joint strategies for clinical research have achieved significant results." Shen Lin, deputy dean of Peking University Cancer Hospital, said that combined immunotherapy is expected to expand the range of patients benefiting from immunotherapy, Improves efficacy and reduces side effects more than a single treatment regimen.
In addition, not all cancer patients are eligible for an immunotherapy. “There have been reports of super-progress cases, and patients have undergone extraordinary rapid progression after receiving anti-PD-1/PD-L1 and other immunological checkpoint inhibitors.†Shen Lin said, to identify which patients can Benefits, which patients may be compromised, require effective biomarkers.
"Better biomarkers can guide patients to choose the right treatment and predict the efficacy." Shen Lin said that there are currently no biomarkers for predicting efficacy, predictive markers for adverse reactions, and lack of predictiveness for super-progressive diseases. Biomarkers.
It can be seen that the immune checkpoint inhibitors need to achieve the "magic drug" level, and also need a series of scientific explorations in the actual treatment, such as the efficacy prediction, therapeutic advancement, etc., in order to achieve the most appropriate precision treatment for cancer patients.
Source: Technology Daily
Photoelectric,Photoelectric Sensor Type,Photoelectric Sensor,Photoelectric Fire Alarm
Guangdong Isafenest Co.,Ltd. , https://www.isfenest.com