New Biological agents for the treatment of systemic Lupus Erythematosus
SLE, also known as systemic lupus erythematosus, is a classic and complex autoimmune disease with multiple systemic involvement. The development of new drugs and the exploration of new therapies are still the focus of attention by scholars.
In recent years, with the development of molecular biology and immunology, many specific biological agents have emerged as the times require for different aspects of the pathogenesis of SLE. As a recombinant product that selectively targets molecules involved in immune or inflammatory processes, or monoclonal antibodies or natural suppressor molecules targeting receptors, the current biological agents used in the treatment of SLE can be classified into five categories according to their mechanisms of action. Specific classifications and the application of various biological agents are as follows:
I. Biological agents for B cells
Rituximab (RTX) is the first biological preparation used to treat SLE. It belongs to the monoclonal antibody against B cell CD20, which can selectively scavenge CD20 B cells and reduce autoantibody production. Currently, about 0.5 to 1.5% of SLE patients in Europe are used outside the drug's indications. Some studies have shown that RTX can effectively improve the clinical manifestations of SLE, including lupus nephritis, neuropsychiatric lupus, vasculitis, and blood system involvement, mainly for SLE, which is intolerable or traditionally ineffective or has severe organ involvement. So that it can get clinical remission, and its tolerance is good and bad. The main reaction is allergy, infection. It is worth noting that RTX alone is not sufficient and should be used in combination with hormones and immunosuppressants.
2. Anti-B Lymphocyte stimulating Factor Inhibitor-Bailey Monoclonal Antibody
Bailey McAb is a humanized IgG1 monoclonal antibody, which can specifically inhibit B lymphocyte stimulating factor, thus inhibit the development and maturation of B cells and induce the apoptosis of B cells. It is the first biological agent approved for the treatment of SLE in recent 50 years. Approved by the United States and the European Union in 2011 for treatment of autoantibody positive adult SLE patients, the 2013 Spanish autoimmune Task Force indicated in its clinical guidelines that Bailimumab could be used in the treatment of SLE, but had not yet been approved domestically. Studies have shown that Pele's McAb can lead to clinical remission, scores, and clinical outcomes in most patients with SLE. The symptoms were improved, the recurrence was delayed, and the safety was good. The relapse rate could be reduced by adding Bailimab on the basis of hormone and immunosuppressant.
3. Anti CD22 Monoclonal Antibody
Epachumab is a humanized monoclonal antibody against CD22, which plays an important role in immunomodulation. The study shows that Epachumab combined with traditional medicine can continuously reduce disease activity and improve the quality of life of patients with moderate and severe SLE, and the incidence of adverse events has not increased.
Second, biological agents that alter the interaction of TnB cells
1. CTLA4-- (Abatacept)
Abasip is a water-soluble and completely humanized CTLA4-IgG1 fusion protein, which can inhibit the synergism between TGB cells. The SLE mouse model has proved that it can inhibit the immune response, thereby reducing the production of autoantibodies and reducing renal lesions. Remission of illness; Some clinical trials showed that it did not show good therapeutic effect compared with placebo, and the adverse reaction increased.
2. Anti CD40L McAb BG9588
The binding of CD40L and CD40 plays an important role in the interaction of Thunb cells and the proliferation and activation of B cells, leading to the production of autoantibodies and renal injury in lupus. BG9588 is a humanized anti CD40L monoclonal antibody. Further study is needed.
3. Anti CD11a Monoclonal Antibody
Legumab is a recombinant human monoclonal antibody against CD11a, which has been shown to be effective in the treatment of subacute cutaneous lupus erythematosus and discoid lupus erythematosus.
III. Biological agents related to immune tolerance
Abelimus (LJP394) is a kind of B cell tolerance, developed by LJP Company. It is a synthetic peptide with triethylene glycol as the skeleton and has immunomodulatory function. It can specifically bind to dsDNA antibody and block its binding to tissues, thus preventing the occurrence of SLE. However, some studies suggest that it has no significant improvement on lupus nephritis and extrarenal symptoms. In addition, intravenous immunoglobulin and recombinant human DNA enzyme treatment of SLE are also under study.
IV. Cytokine related biological agents
1. Anti-tumor necrosis factor inhibitor: infliximab
Infliximab is a specific inhibitor of human mouse chimeric tumor necrosis factor. Current studies have shown that it can improve clinical symptoms and alleviate inflammatory reaction in patients with refractory SLE, but has no effect on autoantibodies, and should be on the alert to induce SLE like syndrome. Its safety and long-term efficacy need to be further evaluated.
Anabelsin, an antagonist of 2.IL-1 receptor
Anabelsin is a recombinant human IL-1 receptor antagonist. Open clinical trials have shown that it can partially improve joint symptoms, but it is easy to recur and has no significant effect on muscle pain. The therapeutic effect of Anabelsin on lupus nephritis is still under study.
3. Anti IL-6-- bracket monoclonal antibody
Todzumab (Tocilizumab) is a recombinant monoclonal antibody against human IL-6 receptor IgG1. It was found in a mouse model of lupus that it can delay the onset of lupus nephritis. The clinical observation showed that the disease activity and anti dsDNA antibody level of SLE were decreased, but the incidence of infection was increased, so the safety need to be further evaluated.
4. Anti IFN-a
Anti IFN-a antibodies: the partial studies including Lollizumab (Rontalizumab) and Xipamurus McAb (Sifalimumab), do not have a clinical end point, and the efficacy and safety of these studies need to be further studied.
Anti-IFN-a receptor antibody: MEDI-546 is an anti-IFN-a receptor antibody, and its clinical trial of SLE treatment is still under way. Immunized IFN-a:IFNa-Kinoid (IFN-K) is an autoimmune vaccine with inactive IFN-a binding to keyhole hemocyanin (KIH). Lupus mouse model studies have shown that it alleviates proteinuria and renal pathological changes. Clinical trials are still under way.
V. other
Ikuzumab is a humanized monoclonal antibody against C5, which can reduce the production of inflammatory mediators and tissue damage by inhibiting the activation of complement C5. Animal experiments show that it can delay renal pathological damage and prolong life, but it should be on guard against infection.
In addition, T-cell vaccines, Toll-like receptor inhibitors, are also being studied. Source: the Department of Rheumatology and Immunology of the second people's Hospital of Guangdong Province
(all contents of this website are indicated as "Huibai Reagent", copyright belongs to Huibai Reagent. Without authorization, no media, website or individual may reprint it. Otherwise, legal liability will be investigated and the authorization to reprint shall be marked "source: Huibai Reagent" . This website indicates the source is other media content is reprinted, reprint only for the viewpoint sharing, the copyright belongs to the original author all, if has the infringement copyright, please contact us in time.
In recent years, with the development of molecular biology and immunology, many specific biological agents have emerged as the times require for different aspects of the pathogenesis of SLE. As a recombinant product that selectively targets molecules involved in immune or inflammatory processes, or monoclonal antibodies or natural suppressor molecules targeting receptors, the current biological agents used in the treatment of SLE can be classified into five categories according to their mechanisms of action. Specific classifications and the application of various biological agents are as follows:
I. Biological agents for B cells
Rituximab (RTX) is the first biological preparation used to treat SLE. It belongs to the monoclonal antibody against B cell CD20, which can selectively scavenge CD20 B cells and reduce autoantibody production. Currently, about 0.5 to 1.5% of SLE patients in Europe are used outside the drug's indications. Some studies have shown that RTX can effectively improve the clinical manifestations of SLE, including lupus nephritis, neuropsychiatric lupus, vasculitis, and blood system involvement, mainly for SLE, which is intolerable or traditionally ineffective or has severe organ involvement. So that it can get clinical remission, and its tolerance is good and bad. The main reaction is allergy, infection. It is worth noting that RTX alone is not sufficient and should be used in combination with hormones and immunosuppressants.
2. Anti-B Lymphocyte stimulating Factor Inhibitor-Bailey Monoclonal Antibody
Bailey McAb is a humanized IgG1 monoclonal antibody, which can specifically inhibit B lymphocyte stimulating factor, thus inhibit the development and maturation of B cells and induce the apoptosis of B cells. It is the first biological agent approved for the treatment of SLE in recent 50 years. Approved by the United States and the European Union in 2011 for treatment of autoantibody positive adult SLE patients, the 2013 Spanish autoimmune Task Force indicated in its clinical guidelines that Bailimumab could be used in the treatment of SLE, but had not yet been approved domestically. Studies have shown that Pele's McAb can lead to clinical remission, scores, and clinical outcomes in most patients with SLE. The symptoms were improved, the recurrence was delayed, and the safety was good. The relapse rate could be reduced by adding Bailimab on the basis of hormone and immunosuppressant.
3. Anti CD22 Monoclonal Antibody
Epachumab is a humanized monoclonal antibody against CD22, which plays an important role in immunomodulation. The study shows that Epachumab combined with traditional medicine can continuously reduce disease activity and improve the quality of life of patients with moderate and severe SLE, and the incidence of adverse events has not increased.
Second, biological agents that alter the interaction of TnB cells
1. CTLA4-- (Abatacept)
Abasip is a water-soluble and completely humanized CTLA4-IgG1 fusion protein, which can inhibit the synergism between TGB cells. The SLE mouse model has proved that it can inhibit the immune response, thereby reducing the production of autoantibodies and reducing renal lesions. Remission of illness; Some clinical trials showed that it did not show good therapeutic effect compared with placebo, and the adverse reaction increased.
2. Anti CD40L McAb BG9588
The binding of CD40L and CD40 plays an important role in the interaction of Thunb cells and the proliferation and activation of B cells, leading to the production of autoantibodies and renal injury in lupus. BG9588 is a humanized anti CD40L monoclonal antibody. Further study is needed.
3. Anti CD11a Monoclonal Antibody
Legumab is a recombinant human monoclonal antibody against CD11a, which has been shown to be effective in the treatment of subacute cutaneous lupus erythematosus and discoid lupus erythematosus.
III. Biological agents related to immune tolerance
Abelimus (LJP394) is a kind of B cell tolerance, developed by LJP Company. It is a synthetic peptide with triethylene glycol as the skeleton and has immunomodulatory function. It can specifically bind to dsDNA antibody and block its binding to tissues, thus preventing the occurrence of SLE. However, some studies suggest that it has no significant improvement on lupus nephritis and extrarenal symptoms. In addition, intravenous immunoglobulin and recombinant human DNA enzyme treatment of SLE are also under study.
IV. Cytokine related biological agents
1. Anti-tumor necrosis factor inhibitor: infliximab
Infliximab is a specific inhibitor of human mouse chimeric tumor necrosis factor. Current studies have shown that it can improve clinical symptoms and alleviate inflammatory reaction in patients with refractory SLE, but has no effect on autoantibodies, and should be on the alert to induce SLE like syndrome. Its safety and long-term efficacy need to be further evaluated.
Anabelsin, an antagonist of 2.IL-1 receptor
Anabelsin is a recombinant human IL-1 receptor antagonist. Open clinical trials have shown that it can partially improve joint symptoms, but it is easy to recur and has no significant effect on muscle pain. The therapeutic effect of Anabelsin on lupus nephritis is still under study.
3. Anti IL-6-- bracket monoclonal antibody
Todzumab (Tocilizumab) is a recombinant monoclonal antibody against human IL-6 receptor IgG1. It was found in a mouse model of lupus that it can delay the onset of lupus nephritis. The clinical observation showed that the disease activity and anti dsDNA antibody level of SLE were decreased, but the incidence of infection was increased, so the safety need to be further evaluated.
4. Anti IFN-a
Anti IFN-a antibodies: the partial studies including Lollizumab (Rontalizumab) and Xipamurus McAb (Sifalimumab), do not have a clinical end point, and the efficacy and safety of these studies need to be further studied.
Anti-IFN-a receptor antibody: MEDI-546 is an anti-IFN-a receptor antibody, and its clinical trial of SLE treatment is still under way. Immunized IFN-a:IFNa-Kinoid (IFN-K) is an autoimmune vaccine with inactive IFN-a binding to keyhole hemocyanin (KIH). Lupus mouse model studies have shown that it alleviates proteinuria and renal pathological changes. Clinical trials are still under way.
V. other
Ikuzumab is a humanized monoclonal antibody against C5, which can reduce the production of inflammatory mediators and tissue damage by inhibiting the activation of complement C5. Animal experiments show that it can delay renal pathological damage and prolong life, but it should be on guard against infection.
In addition, T-cell vaccines, Toll-like receptor inhibitors, are also being studied. Source: the Department of Rheumatology and Immunology of the second people's Hospital of Guangdong Province
(all contents of this website are indicated as "Huibai Reagent", copyright belongs to Huibai Reagent. Without authorization, no media, website or individual may reprint it. Otherwise, legal liability will be investigated and the authorization to reprint shall be marked "source: Huibai Reagent" . This website indicates the source is other media content is reprinted, reprint only for the viewpoint sharing, the copyright belongs to the original author all, if has the infringement copyright, please contact us in time.
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