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Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

ABSTRACT: Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of personalized medicine. In this review article, we provide an overview of the taxonomy, pharmacology, and therapeutic applications of MAbs in glomerular diseases. We searched the literature through PubMed using the following search terms: monoclonal antibodies, glomerular diseases, pharmacokinetics, pharmacodynamics, immunoglobulin, murine, chimeric,humanized, and fully human, and limited our search to years 2018-2023. We selected peer-reviewed journal articles with an evidence-based approach, prioritizing randomized control trials in specific glomerular diseases, if available. Advances in the MAb field have resulted in a significant paradigm shift in targeted treatment of immune-mediated glomerular diseases, and multiple randomized control trials are currently being conducted. Increased recognition is critical to expand their use in experimental research and personalized medicine.

SUBMITTER: Mansour I

PROVIDER: S-EPMC10338194 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Mansour Iyad I Murugapandian Sangeetha S Tanriover Bekir B Thajudeen Bijin B

Mayo Clinic proceedings. Innovations, quality & outcomes 20230630 4

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, re ...[more]

PMID: 37448529

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Project description:We have developed a monoclonal antibody (mAb) C7 that reacts with Als3p and enolase present in Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of mAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in presence of a subinhibitory concentration of mAb C7 (12.5 µg/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with mAb C7. Of these, 28 were found to be up-regulated and 21 down-regulated. The categories of up-regulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the down-regulated genes (8/21). Results were validated by real Time PCR. Since these effects resembled those found under iron-limited conditions, the activity of mAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking TPK1 and TPK2 genes were less sensitive to the candidacidal effect of mAb C7. FeCl3 or hemin at concentrations ≥ 7.8µM reversed the candidacidal effect of mAb C7 on C. albicans, on a concentration dependent manner. The results presented in this study provide evidence that the candidacidal effect of mAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans. A saturated culture of C. albicans grown overnight was diluted to an optical density at 600 nm of approximately 0.1 and divided in two aliquots. One of them was used untreated as control and the second one was treated with a subinhibitory concentration (12.5 µg/ml) of monoclonal antibody C7 . Both cultures were incubated for 18 h at 37ºC before harvesting cells. Antibody added and control samples were obtained each time. The experiment was repeated once. Dye-swap technique was used for hybridization and four arrays were analyzed to compare the expresion of over six thousands genes in response to antibody C7.

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Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Publications

Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

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