Nano-antibodies "small material use" Sanofi, Corning Jerry, Nanjing legend are all developing

Not long ago, Cell published an important paper online on the development of new crown antibodiesScientists have found a variety of "nano-antibodies" in the alpaca that can effectively neutralise the pseudoviruses of SARS, MERS, and the new coronavirus in in vitro experimentsThis research has once again attracted the industry's attention to nano-antibody technologyIn fact, nano-antibodies have great potential and potential for applicationFierce Biotech has named Ablynx' nanoantibody technology platform as the top 10 leading technology platforms in biotechnology pharmaceuticals over the next decadeWhat are nanoantibodies? Simply put, it is a class of antibodies that contain only naturally occurring heavy chains and are much smaller in size than ordinary antibodiesDue to its unique structure, nano-antibodies are the ideal material for the creation of new biopharmaceuticals with a variety of competitive advantagesIn fact, the concept of developing nano-antibodies into drugs has been clinically proven, and the world's first nanoantibody Cablivi (caplacizumab) was approved for sale in the European Union in 2018The discovery of nano-antibodies from camels dates back to the 1980sLike many new drug discoveries, the discovery of nano-antibodies is also very accidentalIt is understood that a student at the Free University of Brussels in Belgium at the time, Muyldermans, complained to his mentor, Professor Hamers, about the lack of challenge in the school's experimental coursesSo Professor Hamers used the remaining half a litre of the fridge to study the sleeping camel's blood and ask them to try to purify the camel's antibodiesAs a result, Muyldermans and others were surprised to find that half of the antibodies purified from camel blood were not the standard type of other vertebrates, but rather a completely new, simpler, special antibodyThis left everyone wondering, and Professor Hamers set up a research team to study the antibodiesInitially, they assumed that the small proteins were just fragments of conventional antibodiesBut fresh camel blood, airlifted from Kenya, also contains the same new antibodies"It's weird, so it took us two years to check that we've made a mistake Professor Hamers recalled In 1993, Muyldermans and his mentor Hamers first reported the properties of nano-antibodies in the journal Nature It is reported that there is a naturally missing light chain antibody in the camel's peripheral blood, which contains only one heavy-chain variable zone (VHH) and two conventional constant zones (CH2, CH3), but is not as easy to stick to each other as the artificially modified single-stranded single-stranded antibody fragments (scFv) and even cluster into blocks The structural analysis results show that the VHH crystal is 2.5nm, 4nm long, relative to the molecular weight is less than 15kDa, and is also called nanoantibodies (Nanobody, Nb) The article mentions that there is a disulfur bond inside the nanoantibodies, and there are a large number of hydrophilic residues on the surface, which has strong resistance to heat and PH values Later studies also found that the new antibody was found not only in camels such as llamas and alpacas, but also in cartilage fish such as nurse sharks, plaque sharks, and silver herrings As for why did these animals evolve such exotic antibodies? It's still a mystery The ideal material for the development of new biopharmaceuticals Is interesting, although there is less light chain variable zone, but nanoantibodies have conventional monodomain antibodies can not be compared with water solubility and structural stability, and can be highly specific, high affinity and binding with antigens, so as to neutralize or close the relatively hidden antigen epithelial In addition, it also has the advantages of low molecular weight, easy expression, not easy to appear space position resistance and so on Based on the special structure of nano-antibodies, and the advantages of traditional antibodies and small molecule drugs, it is an ideal material for the creation of new biological drugs with a variety of competitive advantages At present, nano-antibodies for the development of innovative therapies mainly in the following directions First, the use of nano-antibodies easy to modify the characteristics of the construction of dual-functional antibodies or bispecific antibodies, greatly improve the ability of antibody and antigen binding, so as to more efficient removal of pathogens The world's first approved nanoantibody caplacizumab treats acquired thrombosis reduced cyanosis by binding to the super-large vascular pseudobomophilia factor (vWF) protein in the process of thrombosis, blocking the interaction between the super-large vWF polymer and the platelets, thus preventing clotting The second is the use of nano-antibodies can not only bind to certain drug molecules and through the characteristics of biofilm tissue, so that nano-antibodies carry specific drugs to reach the brain tissue, so as to target the treatment of certain brain diseases Based on this, Ablynx has developed several nano-antibodies that are resistant to Alzheimer's disease This principle is also applicable to the treatment of certain tumors It is reported that enterprises have developed targeted EGFR, HER2, VEGFR2, c-Met, CXCR7 and other anti-tumor nano-antibodies Third, the use of nano-antibody high stability characteristics, used to kill hidden in the cell of the relevant viruses, such as hepatitis B virus, HIV virus In addition, many researchers also use nano-antibodies to treat rotavirus-induced diarrhea, trypanosomiasis, treatment of brucellosis infection and so on Chinese pharmaceutical companies laying out nano-antibodies mention nano-antibodies, and the first thing that comes to mind is the company Thatinnx, which developed the first nano-antibody Cablivi A biopharmaceutical company that specializes in the development of nano-antibody protein drugs, it was acquired by Sanofi in January 2018 for 3.9 billion euros It is reported that Ablynx has developed more than 40 nanoantibody candidate drugs for cancer, autoimmune diseases, respiratory diseases, blood system diseases and many other fields In China, some companies have also begun to explore the field of nano-antibodies, but also related products of clinical development into the later stage Corning Jerry is one of the fastest-growing companies According to the company's official website, it has partnered with the School of Life Sciences of Southeast University to establish an immune-derived camel nanoantibody phage display screening platform, and successfully developed a recombinant humanized PD-L1 monodomain antibody KN035 The product is being conducted in China, the United States and Japan, KN035 is conducting simultaneous clinical trials for multiple tumor indications, as soon as the clinical phase 3, and also the U.S FDA has been granted orphan medicine qualification According to Corning Jerry's announcement, compared to the currently listed PD-1/L1 antibodies, KN035's differentiation advantage is subcutaneous injection, suitable for infusion patients, can greatly improve patient compliance At the same time, it also has the advantages of high affinity, rapid tumor penetration, long retention time, good preparation stability, advanced technology and low cost Prikin Bio, another Chinese biological company focused on nano-antibodies, has built a gene pool of immune nanoantibodies for multiple infections and tumor-targeted antigens, and a nanoantibody gene pool for cell immunity for lung, breast and prostate cancer At THE 2019 ASCO Annual Meeting, the company brought BCMA CAR-T, which carries humanized nano-antibodies, to the attention of the company In the study, 22 patients with recurrent/refractive multiple myeloma (RRMM) received BCMA CAR-T treatment, with an objective mitigation rate of 90.9% and a total remission rate of 36.4% This data on effectiveness and persistence is exciting and promises to provide an entirely new treatment for RRMM patients Nanjing Legend has also developed a nanoantibody LCAR-B38M-CAR-T (also known as JNJ-68284528) for B-cell mature antigen (BCMA) targets, and preliminary clinical research data reflect the unique clinical advantages of monodomain antibodies applied to CAR-T therapy It's worth noting that the product is currently being developed by the company in partnership with Johnson and Johnson, and Phase 3 of the world has been launched The product is expected to be submitted to the U.S listing in the second half of 2020 and a new drug listing application in China in 2021 In addition, Boshengji is also committed to the development of CD7 nanoantibodies immunotoxin and CD7-CAR-NK cell therapy products CD7 is a sensitive marker of T-ALL and a potential target for the treatment of T-ALL According to the company's announcement, its development of CD7 nano-antibodies, with different antibody affinity and antigen identification episomes, can meet the clinical requirements for different levels of CD7 expression of malignant tumors As you can imagine, the future potential of nano-antibodies is enormous and is expected to be used to treat a range of serious and life-threatening diseases In addition to the development of innovative therapies, nano-antibodies are also playing a role in disease diagnosis We look forward to the creation of more innovative therapies based on this area for the early benefit of more patients Originaltitled: Nanoantibodies for "Small MaterialUse", Sanofi, Corning Jerry, Nanjing Legend, etc are all under development