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Humanized Antibodies---a Field with Unlimited Potential

January 15, 2019

Author: chen shanshan

Abstract: From the advent of the monoclonal antibody to the present, it has undergone a tortuous development. Humanized antibodies are an important milestone and are accompanied by a series of major technological innovations such as PCR technology, antibody library technology, and genetically modified animals. The form of the humanized antibody has also evolved from the original chimeric antibody, modified antibody, etc. to today's human antibody. The humanization of antibodies has become the development trend of therapeutic antibodies, and various antibody derivatives are also emerging. They overcome the application limitations of the antibodies themselves from different angles, and provide more tools for treating human diseases. Modification of monoclonal antibodies for clinical treatment requires not only a more in-depth study of the mechanism of antibody action, but also a comprehensive and accurate understanding of the regulatory mechanisms of the human immune system. The greatest feature of an antibody drug is that it recognizes the specificity of the antigen. This article mainly introduces the development history and research progress of therapeutic antibodies, especially humanized antibodies, and summarizes the research status of antibody derivatives. Keywords: humanized antibody, phage antibody library What is a humanized antibody? Humanized antibodies are a transitional form from murine monoclonal antibody to fully human antibodies. On the basis of a mouse monoclonal antibody, the corresponding portion of the murine antibody was replaced with a human antibody constant region to form a human mouse chimeric antibody. About 70% of these antibody molecules are human, retaining the characteristics of the parental antibody in terms of antigen specificity and affinity, while the immunogenicity is reduced to about 12%, and the half-life and effector functions in the body are closer to humans. The murine component is further reduced on the basis of the chimeric antibody, and only the CDR regions of the murine antibody are retained, and the rest are replaced with the corresponding portions of the adult antibody, and the human antibody of the modified antibody is 90%, that is, the humanized antibody generally referred to. It is worth noting that CDR grafting often leads to a decrease in affinity and is not applicable to every murine monoclonal antibody. Preparation of fully human therapeutic antibodies Whole human therapeutic antibodies are the development trend of therapeutic antibodies. At present, the method for producing fully human antibodies has reached a relatively mature stage, mainly including transgenic mouse technology and antibody library technology. Transgenic mouse technology In 1989, Bruggemann et al. successfully transferred the human antibody heavy chain gene library into mice, which produced an immune response to human heavy chain proteins. Subsequently, the technology of transgenic mice continued to develop and improve. In 1994, American transgenic mice were introduced as vectors for the production of fully human antibodies. In 1997, Abgenix successfully used the technology to prepare the transgenic mouse Xenomouse, a genetically engineered mouse that synthesizes antibodies with human protein sequences in vivo. The transgenic mice established by Medarex have developed antibodies for Phase III clinical trials. When the transgenic mouse technology is used to prepare a fully human antibody, since the antibody is produced in vivo and undergoes normal assembly and maturation processes, it has the advantages of high efficacy and strong target affinity. However, there are also some shortcomings. In addition to the complicated operation, high difficulty, high cost and incomplete human sequence, British scholar Clark believes that the antibody produced by the final step of antibody assembly and glycosylation in mice There may be a pattern of glycosylation. Although there is currently no clinical evidence that glycosylation causes any problems, it directly leads to the fact that these monoclonal antibodies are ultimately not fully human. Phage antibody library technology In the 1990s, combinatorial chemistry technology and genetic engineering antibody technology combined to produce antibody library technology. The development of antibody library technology has led to changes in traditional antibody preparation methods, opening up a new world of antibody preparation in vitro, which is currently considered to be the fastest, simple and economical method for preparing human antibodies. The biggest feature of the antibody library In addition to high-throughput screening and screening of antibodies  that are human-derived, and the library capacity is greatly increased, it is theoretically possible to screen specific antibodies against any antigen from these large-capacity human antibody libraries, and to solve some The problem of difficult preparation of antibodies against weak immunogens and toxic antigens. Classification of phage antibody libraries Natural antibody library immune antibody library semi-synthetic antibody library synthetic antibody library Antibody library’s powerful screening capabilities Specific antibodies against an antigen can be screened directly from the library using a phage antibody library. The choice of the best screening method for different antigens is also different. According to the different characteristics of each screening method, two kinds of alternate screening can be selected to improve the screening positive rate. Throughout recent studies, most of the human antibody libraries constructed have relatively simple source of lymphocyte RNA, usually from healthy volunteers or antibody libraries for certain diseases, so that the diversity of antibody libraries is limited. Other antibody library displays In recent years, many other display platform systems have also been used to display antibody libraries, including ribosome display, yeast display, bacterial display, baculovirus display, mammalian cell display, retroviral display, and bacterial periplasmic display. There are also minimal unit display systems such as mRNA displays, DNA display systems, and more. The ribosome display technology frees the display technology from the limitations of the display technology in vivo, and the library capacity is greatly improved, which lays a foundation for high-throughput screening in vitro; The mRNA display technology directly links the mRNA to the expressed protein, so that the screening efficiency is further improved; The DNA display technology DNA template replaces the unstable mRNA to make the display system more stable, and the method is simple and ingenious.   Three techniques have been widely used in antibody screening, affinity maturation, and molecular evolution. Some of the above-mentioned in vitro display technologies are not dependent on any cell system, and are not affected by cloning and cell transformation efficiency, and have a large library capacity, which can make up for the deficiency of traditional in vivo display technology. References  [1] Reichert JM. Antibodies to watch in 2010 [J]. MAbs, 2010, 2(1): 84-100 [2] Nelson AL, Dhimolea E, Richert JM. Development trends for human monoclonal antibody therapeutic [J]. Drug Discovery, 2010, 9:767-774

Vacuum heat treatment furnace

January 15, 2019

Author: lay1014 lay1014

  Theoretical analysis of rapid leakage of vacuum heat treatment furnace Vacuum degree drops quickly, need not consider more commonly, affirmation exists leak point. It is much easier to find the cause of rapid leakage than the trace leakage, and the problem can be solved by the method of theoretical analysis, at most supplemented by a simple leak detection method, the leakage point can be found. The basis of theoretical analysis is data. Without real and detailed data, it is impossible to carry out theoretical analysis. When the vacuum degree of the vacuum heat treatment furnace is abnormal, it is necessary to observe in detail the process of vacuum degree decline, the working condition of the equipment before and after the vacuum degree decline, and the data changes of each indicating instrument on the equipment, including the changes of the backfilling pressure gauge. These data are important basis for theoretical analysis. Sometimes theoretical analysis based on data changes can even directly find the leakage point. The following are two practical examples of finding leakage points by applying theoretical analysis. Someone once in normal operation and in the process of the vacuum degree of vacuum furnace heating area suddenly falling fast, observe the vacuum quenching area basic normal did not change, after the vacuum heating area is lower than the vacuum quenching, vacuum heating area is still falling, vacuum quenching area or normal without big changes, send equipment operator monitor the performance of the equipment heating zone on the vacuum pump, returns are working properly. Process is in the process of pneumatic back, immediately let the equipment the operator to check back to the aeration tank pressure gauge, the changes of aeration tank back pressure in the continuous decline, preliminary confirmation could be back to the charging valve has a problem, let the operator immediately turn off the air supply valve of gasholder, the vacuum degree of heating area then began to rise, which confirmed that really is back to the charging valve leakage caused by heating in vacuum. Standing in the control room to observe the changes in the instrument, send the operator to separate to check the pump and gas tank changes, within 3 minutes to troubleshoot the fault. In fact, I thought a lot at that time. First of all, the failure of the measurement system was eliminated. It will not be caused by the surface of the workpiece in the vacuum chamber, because it will not produce such a large amount of degassing; It must have been a sudden big leak. This kind of leakage hole leakage generally does not occur in the static seal, occurs in the dynamic seal, immediately think of heating zone dynamic seal there are several, the current state of work and which part, since it is in the process of hot zone back inflation, so it is the problem. Maintenance valve after the furnace, fundamentally solve the problem. Another example is the vacuum in the quenching zone. The equipment: by the main rough mechanical pump and roots pump composition of the pumping system, simultaneously connected to the hot and cold areas, when the furnace is first by its pumping hot area, when the hot area reaches a certain degree of vacuum, by it to pumping cold area, and then by the front mechanical pump and diffusion pump composed of the pumping system pumping hot area. Once the furnace is opened, the main rough mechanical pump and roots pump composed of the exhaust system exhaust heat area, and then transferred to the exhaust cooling area, by the front mechanical pump and diffusion pump exhaust heat area of the exhaust system. Hotspot has reached the ultimate vacuum, vacuum and the vacuum can not meet the requirements of cold area, check the work state of pump works, mechanical pump also gas town on a regular basis, a preliminary judge cold area for leaks, hot vacuum is normal, that is not the door in the middle of the problem, if the middle door for leaks, the vacuum degree can improve instead of cold area, because of the hot spots of high vacuum degree, front of mechanical pump and diffusion pump smoke extraction system can help the cold area. The front door is the only moving part in the cold zone. It is suspected that there is a problem with the sealing of the front door. Furthermore, it is the easiest to check the sealing of the front door, and there is no need to dismantle the equipment. Vacuum Induction Sintering Furnace Is Used For Smelting Metal PowderHigh Temperature Industrial Brazing Vacuum Furnace For Metallurgical Industry Подбор цементированного карбидного припояПриборы и инструменты для вакуумной пайки  

Water ring vacuum pump factors affecting the price

January 11, 2019

Author: lay1014 lay1014

  We all know that there are many factors that affect the price of the water ring vacuum pump. Next, we will give you a detailed introduction:The first is the configuration of the model. For different models of vacuum pumps, the price is not the same, and now the water ring vacuum pump in the market is like this, so that we can choose the model we choose or the efficiency of our work. If the price is too cheap, the performance of the water ring vacuum pump can not be guaranteed. If you think about it, if the price is much larger than the same model on the market, we can easily see the quality of the water ring vacuum pump. Absolutely not very high, maybe there is no problem at the time of use, but after a period of time, it will definitely be found that the performance of the water ring vacuum pump itself is not guaranteed. In order to avoid unnecessary maintenance costs, we still have to guarantee our water ring. The quality of the vacuum pump, you can not buy a cheap water ring vacuum pump.In fact, we can easily think of it. We buy water ring vacuum pump equipment to ensure the fast and efficient use of our production, to ensure that our water ring vacuum pump can be used for a long time, the price is expensive, in fact, we all know One point for the price, so we choose the same water ring vacuum pump equipment, can not be alone to see the price, we must consider the relative, such as the configuration of the water ring vacuum pump, performance characteristics, work efficiency, after-sales service It is our warranty time, these are the issues we should consider when purchasing the water ring vacuum pump.Therefore, when people choose the price of water ring vacuum pump, they can't just buy cheap products, they have to choose according to its quality, which will be beneficial to their own use. Water Ring Vacuum Pump For Petrochemical IndustryWater Ring Vacuum Pump For Engraving MachineWater Ring Vacuum Pump Of Distillation PressureVacuum Defoaming With Vacuum Pump  

The Best Means of Purchasing Pet Supplies at a Bargain

January 10, 2019

Author: chen shanshan

The steep rise in the prices of all commodities has become such a crucial problem that people are always on the look out for places where you can purchase goods cheaply. Pet owners are a major clan who also bear the brunt of these issues as pet supplies are very expensive. To try and purchase pet-supplies at a discounted rate has become very popular and the main means of doing this is through pet discount coupons online. Given below are some tips which will help you to purchase pet products at a discounted rate.   Make it a point to get good quality pet supplies - Never settle for low quality stuff which may be less expensive. The net result will be that it will turn out to be hazardous for your beloved pet and you will finally have to dole out a big amount for the visits that you make to the vet. It is not the quality of what you buy for your pet that has to be altered, but the means of purchasing it. Buy pet-supplies at a bargain during the winter months from your nearest pet shop as majority of these shops indulge in a clearance sale in winter. So look around and you will come across pet discount coupons which will aid you in buying goods at a subsidized rate. There have emerged numerous online sites which offer wonderful deals for the supplies that you have been looking for. Online pet shops can provide you with pet supplies at cheaper rate as they do not have to bear overhead expenses like taking care of a shop. Another great advantage is that these online stores get pet supplies at a wholesale rate and sell them even singly at wholesale rates. eBay and Craiglist are other places to look for purchasing pet-supplies at a discounted rate. There may be people who have may be selling off second hand pet supplies which may be procured at a bargain. This is one of the best sites where you will get extremely affordable pet supplies. A little researching on your part will make you realize that there are online websites available from where you can buy pet products at an extremely reasonable rate without even venturing out of your home. This is a great advantage as you do not need to waste your precious time searching out for the best deals or waste your energy either.   Today's world is one where internet is the primary market and all you have to do is just log on to a pet supply site which will bring anything you want to your doorstep at extremely reasonable and affordable rates. Article Source:

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