Modern pharmacological approaches to primary treatment nephrotic syndrome

2020 ◽  
Vol 24 (4) ◽  
pp. 9-20
Author(s):  
Ya. F. Zverev ◽  
A. Ya. Rykunova
Keyword(s):  
Nephrotic Syndrome ◽  
Monoclonal Antibodies ◽  
Mycophenolate Mofetil ◽  
Beneficial Effect ◽  
Pharmacological Activity ◽  
Glucocorticoid Receptors ◽  
Calcineurin Inhibitors ◽  
Mechanisms Of Action ◽  
Immune Mechanism ◽  
Immune Mechanisms

The review is devoted to the consideration of the most common drugs currently used in the treatment of primary nephrotic syndrome. Mechanisms of pharmacological activity of glucocorticosteroids, ACTH, calcineurin inhibitors cyclosporine A and tacrolimus, alkylating compounds cyclophosphamide and chlorambucil, mycophenolate mofetil, levamisole, abatacept, rituximab and a number of other recently created monoclonal antibodies. An attempt is made to separate the immune and non-immune mechanisms of action of the most common drugs, concerning both the impact on the immunogenetics of the noted diseases and the direct impact on the podocytes that provide permeability of the glomerular filtration barrier and the development of proteinuria. It is shown that the immune mechanisms of corticosteroids are caused by interaction with glucocorticoid receptors of lymphocytes, and nonimmune – with stimulation of the same receptors in podocytes. It was found that the activation of adrenocorticotropic hormone melanocortin receptors contributes to the beneficial effect of the drug in nephrotic syndrome. It is discussed that the immune mechanism of calcineurin inhibitors is provided by the suppression of tissue and humoral immunity, and the non-immune mechanism is largely due to the preservation of the activity of podocyte proteins such as synaptopodin and cofilin. Evidence is presented to show that the beneficial effect of rituximab in glomerulopathies is related to the interaction of the drug with the protein SMPDL-3b in lymphocytes and podocytes. The mechanisms of action of mycophenolate mofetil, inhibiting the activity of the enzyme inosine 5-monophosphate dehydrogenase, which causes the suppression of the synthesis of guanosine nucleotides in both lymphocytes and glomerular mesangium cells, are considered. It is emphasized that the effect of levamisole in nephrotic syndrome is probably associated with the normalization of the ratio of cytokines produced by various T-helpers, as well as with an increase in the expression and activity of glucocorticoid receptors. The mechanisms of pharmacological activity of a number of monoclonal antibodies, as well as galactose, the beneficial effect of which may be provided by binding to the supposed permeability factor produced by lymphocytes, are considered.

Elotuzumab in the treatment of relapsed and refractory multiple myeloma

2021 ◽  
Author(s):  
Sebastian Grosicki ◽  
Martyna Bednarczyk ◽  
Agnieszka Barchnicka ◽  
Olga Grosicka
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Clinical Studies ◽  
Mechanisms Of Action ◽  
Incurable Disease ◽  
The Us ◽  
Us Fda ◽  
Humanized Monoclonal Antibodies

Multiple myeloma (MM) is still considered an incurable disease. However, drugs with different mechanisms of action that can improve the efficiency of treatment offer hope. Still, there are concerns about an unacceptable increase in toxicity with such regimens. The results of recently published clinical studies of elotuzumab in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone confirm previous hopes to improve the effect of that treatment. Humanized monoclonal antibodies aimed at SLAMF7 stimulate natural killer cells to fight against MM cells. Elotuzumab used in combination with lenalidomide/dexamethasone or with pomalidomide/dexamethasone is approved by the US FDA to treat patients with relapsed and/or refractory MM. The article is a summary of the recent knowledge about the possibility of using elotuzumab in the treatment of relapsed and/or refractory MM and shows its potential uses in the future.

scholarly journals Monoclonal Antibodies for Cancer Treatment

2021 ◽  
Author(s):  
Annemeri Livinalli ◽  
Taís Freire Galvão
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Standard Of Care ◽  
Mechanisms Of Action ◽  
Clinical Applications ◽  
Human Cancers ◽  
Therapeutic Monoclonal Antibodies

Therapeutic monoclonal antibodies have emerged in the 1990 decade as an important option for cancer treatment. These molecules have a diverse set of clinically relevant antitumor mechanisms, directly targeting tumor cells. It has been established as “standard of care” for several human cancers. This chapter reviews the use of monoclonal antibodies in oncology and introduces available biosimilars. The requirements for biosimilar antibody development, mechanisms of action and current clinical applications for cancer treatment is also presented.

Immunosuppressive Agents on the Horizon

2003 ◽  
Vol 16 (6) ◽  
pp. 434-441 ◽  
Author(s):  
Lisa M. McDevitt
Keyword(s):  
Adverse Effect ◽  
Monoclonal Antibodies ◽  
Organ Transplantation ◽  
Calcineurin Inhibitor ◽  
Immunosuppressive Agents ◽  
Mechanisms Of Action ◽  
Long Term Results ◽  
Allograft Survival ◽  
Adverse Affects

The evolution of immunosuppression in organ transplantation has resulted in decreasing rates of rejection and improved allograft survival. The current successes, however, comes at the price of intense drug monitoring, frequent adverse affects, and long-term toxicity. New immunosuppressive agents offer the hope for decreased toxicity and improved long-term results. This article highlights those novel agents that are currently in late-stage clinical studies including new calcineurin inhibitor analogs and formulations, mycophenolate acid sodium, everolimus, FK-778, FTY720, and various monoclonal antibodies. The diverse mechanisms of action of these agents, coupled with promising efficacy and adverse effect profiles, may land each of them a unique niche for immunosuppression in organ transplantation.

Use of Piezo-Immunosensors in Detecting Antigens and Antibodies Using Quartz Crystal Microbalance (QCM): a Novel Technique for Characterization, Understanding Interactions and Mechanisms of Action and Resistance of Monoclonal Antibodies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5137-5137
Author(s):  
Mohammad Muhsin Chisti ◽  
Justin F. Klamerus ◽  
Norman Leo ◽  
Yupin Shang ◽  
Ishmael Jaiyesimi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Serum ◽  
Real Time ◽  
Clinical Efficacy ◽  
Mechanisms Of Action ◽  
Enzyme Linked Immunosorbent Assay ◽  
Frequency Shifts ◽  
Novel Technique ◽  
Peptide Mimotopes ◽  
New Generation

Abstract Background: Antigens like CD20 antigen, are established targets for antibody therapy with monoclonal antibodies (mAb) like Rituximab. Mixed clinico-pathological responses to mAb have been reported either due to presence of antibodies, rapid clearance or low density of target receptor/antigens. This demands need for an assay to monitor serum mAb therapeutic levels to ensure appropriate dosage. Enzyme-linked immunosorbent assay (ELISA) is still the most widely used technique to detect mAb level in human serum which is expensive and time consuming. Understanding properties and interactions of antigens is quintessential for developing better targeted agents and overcoming resistance. Flow cytometry is still the most widely used technique to detect CD20 level in human serum which is expensive, time consuming and does not reveal any details of interaction between the molecules. We have developed a new innovative biosensor based novel technique to not only monitor levels but also study real time interaction of antigens with antibodies using QCM Piezo-immunosensor. This quantitative label free peptide based assay can be used to characterize cell surface antigen, to study antigen- antibody interactions and obtain understanding of mechanisms of resistance to therapy. Method:Mimotope was used as a substitute for the antigen like CD20 and HER2 receptor protein in QCM assays to detect mAb level. The validation samples were prepared from the standard T solution in 10% human serum at three concentrations (10, 20 and 40 ug/ml). The changes in frequencies (ΔF) of sera from 3 female patients were obtained by calculating the differences between frequency shifts in pre and post mAb infusion. mAb level was calculated by equation, (ΔF +1.0022) ÷ 0.9997 μg / ml. The real-time processes of attachment of Cells like Raji cells on the gold electrode and the subsequent binding of antibody like Rituximab to the cells were studied using QCM biosensor. The interaction between Antigen and Antibody led to the increased resonant frequency shifts (df0) in the studied antibody concentration range from 5 to 250 μg mL-1 . Control experiments using other therapeutic antibodies (i.e., Trastuzumab and Bevacizumab) and different cells (i.e., T cells and endothelial cells) proved very specific interaction between Rituximab and CD20 antigens on B cells Results: Antigen and Antibody binding was very specific. This binding decreased the electrochemical activity and stability of the cells, supporting the cell lysis mechanisms of action of Rituximab. We showed that assay sensitivity was dependent upon the amino acids used to tether and link the peptide to the sensor surface and the buffers used. QCM assay was capable of detecting mAb like Trastuzumab serum level as low as 0.038 nM (linear operating range of 0.038-0.859 nM). The time frame of assay was 20-30 minutes. These results were in concordance with previously published results using ELISA. We have shown a systematic approach for using QCM technique to quantify the apparent binding constant between antigen and antibody can reveal antigen density. Conclusion: We have established a low cost, highly sensitive, fast, synthetic peptide based QCM assay which could be used as a basis for developing a new generation of affinity-based Immunosensor assays to monitor mAb serum levels like Rituximab, Trastuzumab and other monoclonal antibodies, helping physicians to determine the clinical efficacy of these drugs and ensuring appropriate dosages. Moreover antigen density and interactions of antigens with respective monoclonal antibodies like CD20 with Rituximab will help physicians to determine the clinical efficacy and resistance mechanisms to targeted antibodies like Rituximab and Ofatumumab. This could be used as a basis for developing a new generation of affinity-based Immunosensor assays. Our study shows that peptide mimotopes have potential benefit in sensor applications as the peptide-peptide interactions in the peptide mimotopes could be manipulated by the addition of functional groups to the peptide to influence binding of the target protein as well as for surface immobilization. Disclosures No relevant conflicts of interest to declare.

Monoclonal antibodies in immunotherapy

2019 ◽  
Vol 1 (1) ◽  
pp. 26-31
Author(s):  
Roy Jefferis
Keyword(s):  
Monoclonal Antibodies ◽  
Cost Effective ◽  
Mechanisms Of Action ◽  
Cellular Immunotherapy ◽  
Human Antibody ◽  
Evidence Based ◽  
Patient Stratification ◽  
Drug Conjugates ◽  
Cost Effective Treatment ◽  
Antibody Drug

The bench-to-bedside ideal is being realised for both humoral and cellular immunotherapy. Monoclonal antibodies (mAbs) are established in the clinic, but continuous development has resulted in progression from mouse/human chimeric to humanised, ‘fully’ human, antibody–drug conjugates, biosimilars and biobetter therapeutics. The objective has been to minimise their potential for immunogenicity and to elucidate and exploit their multiple mechanisms of action (MoA). However, exploitation of these advances within the NHS is limited due their high cost. Consequently, the National Institute for Health and Care Excellence (NICE) offers evidence-based recommendations for the availability of approved mAbs, and other ‘speciality drugs’ within the NHS; alternative avenues for funding may be available while the efficacy of such drug is being fully evaluated. More cost-effective treatment is being achieved through patient stratification following genome sequencing and identification of polymorphisms that predispose people to disease susceptibilities and their responses to particular drugs or combinations of therapeutics.

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