Displaying publications 1 - 20 of 219 in total

  1. Lim TS
    Curr Pharm Des, 2016 10 27;22(43):6477-6479.
    PMID: 27781936 DOI: 10.2174/1381612822999161019110228
    Matched MeSH terms: Antibodies, Monoclonal/genetics; Antibodies, Monoclonal/immunology*
  2. Lee J, Kim YE, Kim HY, Sinniah M, Chong CK, Song HO
    Sci Rep, 2015;5:18077.
    PMID: 26655854 DOI: 10.1038/srep18077
    High levels of anti-dengue IgM or IgG can be detected using numerous rapid diagnostic tests (RDTs). However, the sensitivity and specificity of these tests are reduced by changes in envelope glycoprotein antigenicity that inevitably occur in limited expression systems. A novel RDT was designed to enhance diagnostic sensitivity. Dengue viruses cultured in animal cells were used as antigens to retain the native viral coat protein. Monoclonal antibodies (mAbs) were then developed, for the first time, against domain I of envelope glycoprotein (EDI). The anti-dengue EDI mAb was employed as a capturer, and EDII and EDIII, which are mainly involved in the induction of neutralizing antibodies in patients, were fully available to bind to anti-dengue IgM or IgG in patients. A one-way automatic blood separation device prevented reverse migration of plasma and maximize the capture of anti-dengue antibodies at the test lines. A clinical evaluation in the field proved that the novel RDT (sensitivities of 96.5% and 96.7% for anti-dengue IgM and IgG) is more effective in detecting anti-dengue antibodies than two major commercial tests (sensitivities of 54.8% and 82% for SD BIOLINE; 50.4% and 75.3% for PanBio). The innovative format of RDT can be applied to other infectious viral diseases.
    Matched MeSH terms: Antibodies, Monoclonal*
  3. Choong YS, Lee YV, Soong JX, Law CT, Lim YY
    Adv Exp Med Biol, 2017;1053:221-243.
    PMID: 29549642 DOI: 10.1007/978-3-319-72077-7_11
    The use of monoclonal antibody as the next generation protein therapeutics with remarkable success has surged the development of antibody engineering to design molecules for optimizing affinity, better efficacy, greater safety and therapeutic function. Therefore, computational methods have become increasingly important to generate hypotheses, interpret and guide experimental works. In this chapter, we discussed the overall antibody design by computational approches.
    Matched MeSH terms: Antibodies, Monoclonal/adverse effects; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/therapeutic use*; Antibodies, Monoclonal/chemistry
  4. Chan SK, Lim TS
    Adv Exp Med Biol, 2017;1053:61-78.
    PMID: 29549635 DOI: 10.1007/978-3-319-72077-7_4
    The incident of two children in Europe who died of diphtheria due to a shortage of anti-toxin drugs has highlighted the need for alternative anti-toxins. Historically, antiserum produced from immunised horses have been used to treat diphtheria. Despite the potential of antiserum, the economical and medial concerns associated with the use of animal antiserum has led to its slow market demise. Over the years, new and emerging infectious diseases have grown to be a major global health threat. The emergence of drug-resistant superbugs has also pushed the boundaries of available therapeutics to deal with new infectious diseases. Antibodies have emerged as a possible alternative to combat the continuous onslaught of various infectious agents. The isolation of antibodies against pathogens of infectious diseases isolated from immune libraries utilising phage display has yielded promising results in terms of affinities and neutralizing activities. This chapter focuses on the concept of immune antibody libraries and highlights the application of immune antibody libraries to generate antibodies for various infectious diseases.
    Matched MeSH terms: Antibodies, Monoclonal/biosynthesis; Antibodies, Monoclonal/genetics*; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/therapeutic use
  5. Chua GK
    Prep Biochem Biotechnol, 2016 Oct 02;46(7):679-85.
    PMID: 26760282 DOI: 10.1080/10826068.2015.1135450
    Statistically designed experiments were used in developing a low-serum medium for the production of a diagnostic monoclonal antibody against congenital adrenal hyperplasia using hybridoma 192. A two-level half-fractional factorial design was used for screening six components (Minimum Essential Medium Eagle amino acids, 2-mercaptoethanol, ethanolamine, ferric citrate, zinc sulfate, and sodium selenite). The experimental design was then augmented to central composite design. The basal Dulbecco's modified Eagle's medium (DMEM; containing 4 mM L-glutamine, 1% antibiotic-antimycotic agent) supplemented with 0.4% by volume fetal bovine serum (FBS), 311.8 mM ferric citrate, 17.3 nM sodium selenite, and 4.5 mM zinc sulfate (LSD) was found to support the growth of the hybridoma. Specific cell growth rate in the LSD (0.033 ± 0.001/h) was slightly lower than in the control medium (i.e., basal DMEM supplemented with 2% FBS; 0.0045 ± 0.003/h). Nevertheless, the specific MAb production rate for LSD was higher (0.057 ± 0.015 pg/cell · h versus 0.004 ± 0.002 pg/cell · h in LSD and control, respectively). The antibody produced in the LSD showed high specificity and no cross-reactivity with the other structural resemblance's steroid hormones, revealing no structural changes owing to the new medium formulation developed. The new medium formulation effectively reduced the medium cost by up to 64.6%.
    Matched MeSH terms: Antibodies, Monoclonal/biosynthesis*; Antibodies, Monoclonal/immunology
  6. Ghagane SC, Puranik SI, Gan SH, Hiremath MB, Nerli RB, Ravishankar MV
    Hum Antibodies, 2017;26(3):135-142.
    PMID: 29060935 DOI: 10.3233/HAB-170331
    With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.
    Matched MeSH terms: Antibodies, Monoclonal/immunology*
  7. Palace J, Wingerchuk DM, Fujihara K, Berthele A, Oreja-Guevara C, Kim HJ, et al.
    Mult Scler Relat Disord, 2021 Jan;47:102641.
    PMID: 33310418 DOI: 10.1016/j.msard.2020.102641
    BACKGROUND: Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT.

    METHODS: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.

    RESULTS: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.

    CONCLUSION: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.

    TRIAL REGISTRATION: NCT01892345 (ClinicalTrials.gov).

    Matched MeSH terms: Antibodies, Monoclonal, Humanized/therapeutic use
  8. Kow CS, Hasan SS
    Pulmonology, 2020 10 21;27(1):86-87.
    PMID: 33158786 DOI: 10.1016/j.pulmoe.2020.10.004
    Matched MeSH terms: Antibodies, Monoclonal, Humanized
  9. Bashokouh F, Abbasiliasi S, Tan JS
    Cytotechnology, 2019 Jul 16.
    PMID: 31312930 DOI: 10.1007/s10616-019-00330-5
    Monoclonal antibody (McAb) has been established as one of the most successful therapeutic strategies for the treatment of cancer. M1A2 (McAb) as a new monoclonal antibody was designed to recognize heat shock protein (HSP60), but its optimum production condition has not been studied. In this study, the cell culture conditions for both Roswell Park Memorial Institute Medium (RPMI 1640) and Dulbecco's Modified Eagle Medium (DMEM) were optimized using artificial neural network (ANN) analysis to obtain maximum production of IgM McAb by hybridoma M1A2 cells. By using a central composite design, an experimental matrix with cultivation parameters of incubation time, temperature and fetal bovine serum (FBS) concentration on IgM McAb production was designed. The results was analysed by ANN network with different learning algorithms. From the analysis, batch back propagation (BBP) trained ANN composed of eight hidden nodes using a hyperbolic tangent sigmoid transfer function was capable to provide the highest McAb production for both RPMI and DMEM media. Under optimum conditions of 12.5% of FBS, at 33 °C after 3(1/2) days of incubation, maximum McAb production (1132.69 μg/ml) in DMEM was achieved. With PRMI 1640 medium, maximum McAb production (1105.12 μg/ml) was achieved at optimum conditions of 11% of FBS, at 33 °C after 4 days of incubation. The results of this study will provide information for optimum culture conditions of M1A2 McAb production in both DMEM and RPMI 1640 media and also give some clues for the other hybridoma excreting antibodies in the development of in vitro cell culture.
    Matched MeSH terms: Antibodies, Monoclonal
  10. Lim CC, Choong YS, Lim TS
    Int J Mol Sci, 2019 Apr 15;20(8).
    PMID: 30991723 DOI: 10.3390/ijms20081861
    Antibodies leverage on their unique architecture to bind with an array of antigens. The strength of interaction has a direct relation to the affinity of the antibodies towards the antigen. In vivo affinity maturation is performed through multiple rounds of somatic hypermutation and selection in the germinal centre. This unique process involves intricate sequence rearrangements at the gene level via molecular mechanisms. The emergence of in vitro display technologies, mainly phage display and recombinant DNA technology, has helped revolutionize the way antibody improvements are being carried out in the laboratory. The adaptation of molecular approaches in vitro to replicate the in vivo processes has allowed for improvements in the way recombinant antibodies are designed and tuned. Combinatorial libraries, consisting of a myriad of possible antibodies, are capable of replicating the diversity of the natural human antibody repertoire. The isolation of target-specific antibodies with specific affinity characteristics can also be accomplished through modification of stringent protocols. Despite the ability to screen and select for high-affinity binders, some 'fine tuning' may be required to enhance antibody binding in terms of its affinity. This review will provide a brief account of phage display technology used for antibody generation followed by a summary of different combinatorial library characteristics. The review will focus on available strategies, which include molecular approaches, next generation sequencing, and in silico approaches used for antibody affinity maturation in both therapeutic and diagnostic applications.
    Matched MeSH terms: Antibodies, Monoclonal/genetics*; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/chemistry
  11. Kim HJ, Nakashima I, Viswanathan S, Wang KC, Shang S, Miller L, et al.
    Mult Scler Relat Disord, 2021 May;50:102849.
    PMID: 33676197 DOI: 10.1016/j.msard.2021.102849
    Background Eculizumab, a terminal complement inhibitor, significantly reduced the risk of relapse compared with placebo in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the PREVENT trial. We report efficacy and safety analyses in Asian patients in PREVENT and its open-label extension (OLE). Methods PREVENT was a double-blind, randomized, phase 3 trial. Patients with AQP4+ NMOSD were randomly assigned (2:1) to receive intravenous eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Patients who completed PREVENT could receive eculizumab in an OLE. Analyses were performed in a prespecified subgroup of Asian patients. Results Of 143 patients enrolled, 52 (36.4%) were included in the Asian subgroup (eculizumab, n = 37; placebo, n = 15); 45 Asian patients received eculizumab in the OLE. Most Asian patients (86.5%) received concomitant immunosuppressive therapy. During PREVENT, one adjudicated relapse occurred in patients receiving eculizumab and six occurred in patients receiving placebo in the Asian subgroup (hazard ratio, 0.05; 95% confidence interval: 0.01-0.35; p = 0.0002). An estimated 95.2% of Asian patients remained relapse-free after 144 weeks of eculizumab treatment. Upper respiratory tract infections, headache, and nasopharyngitis were the most common adverse events with eculizumab in the Asian subgroup. Conclusion Eculizumab reduces the risk of relapse in Asian patients with AQP4+ NMOSD, with a benefit-risk profile similar to the overall PREVENT population. The benefits of eculizumab were maintained during long-term therapy. Clinical trial registration ClinicalTrials.gov identifiers: NCT01892345 (PREVENT); NCT02003144 (open-label extension).
    Matched MeSH terms: Antibodies, Monoclonal, Humanized
  12. Kow CS, Hasan SS
    Chest, 2021 05;159(5):2108-2109.
    PMID: 33965134 DOI: 10.1016/j.chest.2020.11.073
    Matched MeSH terms: Antibodies, Monoclonal, Humanized
  13. Chan SK, Rahumatullah A, Lai JY, Lim TS
    Adv Exp Med Biol, 2017;1053:35-59.
    PMID: 29549634 DOI: 10.1007/978-3-319-72077-7_3
    Many countries are facing an uphill battle in combating the spread of infectious diseases. The constant evolution of microorganisms magnifies the problem as it facilitates the re-emergence of old infectious diseases as well as promote the introduction of new and more deadly variants. Evidently, infectious diseases have contributed to an alarming rate of mortality worldwide making it a growing concern. Historically, antibodies have been used successfully to prevent and treat infectious diseases since the nineteenth century using antisera collected from immunized animals. The inherent ability of antibodies to trigger effector mechanisms aids the immune system to fight off pathogens that invades the host. Immune libraries have always been an important source of antibodies for infectious diseases due to the skewed repertoire generated post infection. Even so, the role and ability of naïve antibody libraries should not be underestimated. The naïve repertoire has its own unique advantages in generating antibodies against target antigens. This chapter will highlight the concept, advantages and application of human naïve libraries as a source to isolate antibodies against infectious disease target antigens.
    Matched MeSH terms: Antibodies, Monoclonal/biosynthesis; Antibodies, Monoclonal/genetics*; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/therapeutic use
  14. Dharshanan S, Hung CS
    Methods Mol Biol, 2014;1131:105-12.
    PMID: 24515462 DOI: 10.1007/978-1-62703-992-5_7
    Generation of high-producing clones is a perquisite for achieving recombinant protein yields suitable for biopharmaceutical production. However, in many industrially important cell lines used to produce recombinant proteins such as Chinese hamster ovary, mouse myeloma line (NS0), and hybridomas, only a minority of clones show significantly above-average productivity. Thus, in order to have a reasonable probability of finding rare high-producing clones, a large number of clones need to be screened. Limiting dilution cloning is the most commonly used method, owing to its relative simplicity and low cost. However the use of liquid media in this method makes the selection of monoclonal hybridoma and transfectoma colonies to be labor intensive and time consuming, thus significantly limiting the number of clones that can be feasibly screened. Hence, we describe the use of semisolid media to immobilize clones and a high-throughput, automated colony picker (ClonePix FL) to efficiently isolate monoclonal high-producing clones secreting monoclonal antibodies.
    Matched MeSH terms: Antibodies, Monoclonal/metabolism
  15. Chong H, Cheah SH, Ragavan M, Johgalingam VT
    J Immunoassay Immunochem, 2009;30(2):166-79.
    PMID: 19330642 DOI: 10.1080/15321810902782863
    An indirect enzyme immunoassay for the measurement of total 17alpha-hydroxyprogesterone (17OHP) in serum using monoclonal antibodies generated in our laboratory was developed. Here, (a) instead of extraction with solvents, serum was heated to free protein-bound 17OHP and assay was performed at pH 9.6, (b) to ensure uniform assay conditions for both standards and samples, buffer for standards contained charcoal-stripped pre-heated pooled cord serum. Assays were done in 96-well EIA microplates pre-coated with 17alpha-hydroxyprogesterone-3-(o-carboxymethyl)oxime: bovine serum albumin. Secondary antibody was horseradish peroxidase-linked sheep anti-mouse IgG polyclonal antibody. The method was accurate and suitable for screening for congenital adrenal hyperplasia.
    Matched MeSH terms: Antibodies, Monoclonal/immunology*
  16. Edwards S, Sands JJ
    DTW. Dtsch. Tierarztl. Wochenschr., 1990 Feb;97(2):79-81.
    PMID: 2178905
    Nineteen monoclonal antibodies (MAbs) with specificity for hog cholera virus (HCV) were prepared. They were used in an immune binding (peroxidase linked) assay to determine the reaction patterns of HCV isolates from Europe, Brazil, USA, Japan and Malaysia, as well as laboratory reference strains of the virus. A further panel of 17 MAbs raised against bovine virus diarrhoea virus (BVDV) was included in the study, together with 5 MAbs raised against a non-HCV pestivirus of porcine origin. All the MAbs were also tested against representative strains of BVDV and border disease virus. Six MAbs were HCV-specific, reacting with all isolates of HCV and none of the ruminant viruses. Among the other HCV MAbs geographical variation in reaction patterns was observed. There was evidence of antigenic distinction between recent European isolates, and archive material originally isolated more than 10 years ago.
    Matched MeSH terms: Antibodies, Monoclonal/immunology*
  17. Tan HT, Sugita K, Akdis CA
    Curr Allergy Asthma Rep, 2016 10;16(10):70.
    PMID: 27613653 DOI: 10.1007/s11882-016-0650-5
    PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP).

    RECENT FINDINGS: The biologicals that have been currently approved for asthma are omalizumab targeting IgE and reslizumab and mepolizumab targeting interleukin (IL)-5. Many other monoclonal antibodies are currently in various phases of clinical development. The new biological therapies for allergic diseases will eventually be tailored to the endotypes of these diseases and the identification of novel biomarkers. Further development of novel biologicals for the treatment of allergic diseases and asthma will be possible upon improved understanding of mechanisms of allergic diseases. Accordingly, further refinement of endotypes of allergen-specific and non-specific type 2 immune response and related inflammatory mediators is needed for optimal treatment of allergic diseases.

    Matched MeSH terms: Antibodies, Monoclonal/therapeutic use*
  18. Albela H, Begum S, Leong KF
    J Dermatolog Treat, 2021 Mar 11.
    PMID: 33706651 DOI: 10.1080/09546634.2021.1899111
    Generalized Pustular Psoriasis (GPP) is a rare, severe, life-threatening form of psoriasis and accounts for up to 13.1% of all childhood psoriasis. Common first-line systemic treatment for pediatric patients with GPP include oral acitretin, cyclosporin and methotrexate which have varying efficacy and side effects but multiple interventions are often needed to induce remission and maintain long term control. Recently, the anti IL 17 A monoclonal antibody secukinumab have been shown to be effective in adult patients with GPP; however, there is lack of evidence of its usage in the pediatric population. We describe a case series of 4 pediatric patients with GPP who were treated with off-label use of secukinumab. All four patients had marked clearance and reduction in Generalized Pustular Psoriasis Area & Severity Score (GPPASI) within first 48 h of first injection with subsequent almost complete to complete clearance of skin lesions by 1 month follow up. In conclusion, secukinumab was found to be successful in inducing remission, with rapid clearance and maintaining remission, with or without combination with other systemic agents for pediatric GPP.
    Matched MeSH terms: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized
  19. Ratanam M, Ngim YS, Khalidin N, Subrayan V
    Br J Haematol, 2015 Aug;170(3):431-4.
    PMID: 25640801 DOI: 10.1111/bjh.13307
    Matched MeSH terms: Antibodies, Monoclonal, Humanized/administration & dosage*
  20. Kow CS, Hasan SS
    Eur J Clin Pharmacol, 2021 Aug;77(8):1089-1094.
    PMID: 33532896 DOI: 10.1007/s00228-021-03087-z
    OBJECTIVE: We aimed to perform a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of tocilizumab on the risk of mortality among patients with coronavirus disease 2019 (COVID-19).

    METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and medRxiv (preprint repository) databases (up to 7 January 2021). Pooled effect sizes with 95% confidence interval (CI) were generated using random-effects and inverse variance heterogeneity models. The risk of bias of the included RCTs was appraised using version 2 of the Cochrane risk-of-bias tool for randomized trials.

    RESULTS: Six RCTs were included: two trials with an overall low risk of bias and four trials had some concerns regarding the overall risk of bias. Our meta-analysis did not find significant mortality benefits with the use of tocilizumab among patients with COVID-19 relative to non-use of tocilizumab (pooled hazard ratio = 0.83; 95% CI 0.66-1.05, n = 2,057). Interestingly, the estimated effect of tocilizumab on the composite endpoint of requirement for mechanical ventilation and/or all-cause mortality indicated clinical benefits, with some evidence against our model hypothesis of no significant effect at the current sample size (pooled hazard ratio = 0.62; 95% CI 0.42-0.91, n = 749).

    CONCLUSION: Despite no clear mortality benefits in hospitalized patients with COVID-19, tocilizumab appears to reduce the likelihood of progression to mechanical ventilation.

    Matched MeSH terms: Antibodies, Monoclonal, Humanized/therapeutic use*
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