Human cytomegalovirus (HCMV), also known as human herpes virus type 5, is one of the eight herpes viruses infected by human beings. It has a strict host specificity, resulting in a large infection cell and the appearance of a large eosinophil inclusion body in the nucleus.
The positive proportion of cytomegalovirus in our population is as high as 97%. CMV virus lurks all life after the first infection. People with normal immunity usually do not show clinical pathological symptoms, but for people with low immunity, such as organ transplant recipients, it will cause organ damage caused by large amount of virus propagation and CMV infection. It is the most common virus infection caused by the use of immunosuppressive agents after organ transplantation. If no prevention is carried out, up to 75% of the body organ transplant recipients will appear new infection or latent CMV activation within 3 months after transplantation, and eventually lead to organ transplantation failure or even death.
Therefore, CMV infection is also known as the “death killer” of organ transplant recipients. In addition, congenital infection of HCMV is also the main cause of children’s nervous hearing impairment and central nervous system injury in children. In view of the serious harm of HCMV, all countries in the world attach great importance to the research and development of therapeutic and preventive antibodies and vaccines against HCMV infection.
At present, the chemical drugs used to treat hCMV infection are by inhibiting viral DNA polymerase to inhibit the replication of virus DNA, and renal toxicity often leads to non long-term use of body organ transplant patients. In addition, the continuous use of small molecular drugs has accelerated the emergence of virus resistance. The single mutation or joint mutation of UL97 and UL54 genes leads to drug resistance of small molecules, which seriously reduces the drug treatment and prognosis of patients.
Cytomegalovirus immunoglobulin (CMVIG) of human cytomegalovirus (HCMV) is a plasma protein product rich in high efficiency anti cytomegalovirus neutralization antibody prepared by isolation, purification and virus inactivation. The fusion of hCMV membrane protein mediated virus and cell membrane prevents the virus from invading the host cell and interferes with the replication of the progeny virus, and the neutralization antibody can also induce the Fc receptor mediated modulation to clear the hCMV after the neutralization antibody is combined with the virus.
CMVIG is used to prevent and treat HCMV infection, and has achieved good clinical effect in the application of preventing hCMV infection after solid organ transplantation. Currently, there are only 3 CMVIG products listed worldwide, namely, the Cytogam (CSL Behring) in the United States, the Biotest AG in Europe (Biotest AG) and the Australian Red Cross Blood Service Center (CMVIG).
However, because human anti hCMV immunoglobulin belongs to the blood products, it is difficult to meet the demand of the market in the aspects of blood supply, production cost, batch difference and price control.
At present, there is no relevant human anti hCMV specific immunoglobulin in China. In addition, because the specific immunoglobulin comes from the human blood and is a high risk plasma product, because of the existence of “window period”, these products have the risk of transmitting blood pathogens such as AIDS virus, hepatitis B virus, hepatitis C virus and other unknown viruses.
Compared with hCMV immunoglobulin, monoclonal antibodies have shown very good prospects in recent years. Monoclonal antibody is a recombinant protein drug, which is completely produced at the level of serum-free cells. Therefore, the production process will completely eliminate the social problems, economic costs and the possibility of spreading human pathogens caused by blood collection. The cost of the total human monoclonal antibody was about 1/20 of the traditional Human Immunoglobulin, and the neutralization titer of all human antibody drugs was about 2-3 times that of the traditional Human Immunoglobulin.
As a result of the iteration and development of antibody technology, the fourth generation of natural all human monoclonal antibodies (Native all-Humanantibodies), represented by HitMab technology, have come to the fore. The main techniques of natural total human antibody include human myeloma cell technology, B cell immortalization Technology (EBV transformation B cell clone and other cytokine assisted B cell clone), single B cell RT-PCR and single B cell sequencing technology. This technique is based on the starting point of B cells from human body and finally obtained by single B cells. A useful antibody. In recent years, the fourth generation antibody technology, represented by the human single B cell cloning technology platform, has come to the fore, although there are still a variety of problems, but the technical field is changing the new moon. At present, there are several companies, such as Aridis, iRepertoire, AIMM, Xbiotech, Humabs (Vir Biotechnology subsidiary), Neurimmune and Trinomab (China, Zhuhai), which have mastered the technology of natural all human monoclonal antibody.
The main characteristics of the natural human monoclonal antibody are: not only the gene sequence 100% is human, the antibody heavy chain and light chain are natural primary pairing combination, and its affinity and specificity are mature under the immune tolerance environment of the human body, without autoimmunity, which is called the natural whole human antibody. There is no doubt that natural whole human antibodies will greatly reduce R & D risks and clinical adverse reactions. At present, a number of natural all human monoclonal antibodies against hCMV are in the clinical study stage, such as the CMV monoclonal antibody CSJ-148 developed by Novartis and the MSL-109 developed by JohnHopkins for the prevention of CMV infection after organ transplantation.
Zhuhai Trinomab (Trinomab) Biotechnology Co., Ltd., is a high-tech company created by Dr. Liao Huaxin and Mr. Zheng Weihong, a specialist in the development of natural all human monoclonal antibodies by Dr. Liao Huaxin and Mr. Zheng Weihong. The core technology of the company is the natural whole human monoclonal antibody technology platform (HitMab). The monoclonal antibody produced by the technology platform is a real natural total human monoclonal antibody. Its main technical route is to collect volunteer PBMC, select single B cells, single plasma cells, or single B cell culture by flow cytometry, to obtain specific cells, and then obtain specific molecular biology techniques to obtain specific biological techniques. The antibody gene was finally verified by expressing recombinant antibody. The whole experimental process has achieved “high throughput”, “high efficiency” and “operable”, which can quickly obtain effective natural whole human monoclonal antibodies. At present, the company has developed a variety of natural total human monoclonal antibodies against infectious diseases, which are expected to replace human specific immunoglobulin for the prevention and treatment of infectious diseases in the future.
A few days ago, Zhuhai Tylenol Microlab Biotechnology Co., Ltd. screened and obtained dozens of natural human monocyclic antibodies against hCMV from the fourth generation of “high throughput natural human monoclonal antibody research and development integrated technology platform (HitmAb)) from the volunteer memory B lymphocytes of serum antibody positive, and selected gB and gH sugar eggs. White high school and titer monoclonal antibodies are used to prevent and treat HCMV infection.
The monoclonal antibody obtained by HitmAb technology is a single large molecular product of gene recombination. It is suitable for large-scale production under strict quality control and has good pharmacoeconomic value. Therefore, once the McAb of natural whole human anti cytomegalovirus (McAb) antibody is listed, it will greatly improve the life of the patients with solid organ transplantation. Survival rate will bring huge economic and social benefits.