Sanquin Health Solutions’ Post

In a newly posted pre-print, The University of Georgia authors report that one N-glycan regulates natural killer cell antibody-dependent cell-mediated cytotoxicity and modulates Fc γ receptor IIIa / CD16a structure. From the abstract: Both endogenous antibodies and a subset of antibody therapeutics engage Fc gamma receptor (FcγR)IIIa / CD16a to stimulate a protective immune response. To define the role of individual amino acid and N-glycan residues we measured affinity using multiple FcγRIIIa glycoforms. We observed stepwise affinity increases with each glycan truncation step with the most severely truncated glycoform displaying the highest affinity. Removing the N162 glycan demonstrated its predominant role in regulating antibody-binding affinity, in contrast to four other FcγRIIIa N-glycans. We next evaluated the impact of the N162 glycan on NK cell ADCC. NK cells expressing the FcγRIIIa V158 allotype exhibited increased ADCC following kifunensine treatment to limit N-glycan processing. Notably, an increase was not observed with cells expressing the FcγRIIIa V158 S164A variant that lacks N162 glycosylation, indicating the N162 glycan is required for increased NK cell ADCC. To gain structural insight into the mechanisms of N162 regulation, we applied a novel protein isotope labeling approach in combination with solution NMR spectroscopy. FG loop residues proximal to the N162 glycosylation site showed large chemical shift perturbations following glycan truncation. These data support a model for the regulation of FcγRIIIa affinity and NK cell ADCC whereby composition of the N162 glycan stabilizes the FG loop and thus the antibody-binding site. https://lnkd.in/efkaCuki

👏 A recent study successfully demonstrated the feasibility of 𝐝𝐞 𝐧𝐨𝐯𝐨 𝐩𝐫𝐨𝐭𝐞𝐢𝐧 𝐬𝐞𝐪𝐮𝐞𝐧𝐜𝐢𝐧𝐠 from a human serum polyclonal antibody (pAb), generating multiple monoclonal antibodies (mAbs) that closely resemble the original pAb. The researchers present a method for sequencing human plasma-derived polyclonal IgG using a combination of mass spectrometry and B-cell sequencing. This achievement emphasizes the potential of pAb de novo protein sequencing as a valuable strategy for harnessing the natural immune response of animals and humans, enabling the discovery of antibody reagents and therapeutics. Read the full paper at Nature Portfolio: https://lnkd.in/gZeKGk_j #Biointron #Antibodies #Immunotherapy #Sequencing #Polcylonal

The trajectory of the mRNA modality is set to keep rising. Post-COVID-19 and the deployment of mRNA vaccines against the infectious disease, biopharma, and academic and industry groups have programs to expand mRNA use to other human diseases. Want to learn more about the mRNA modality? Access a free, three-module course from Moderna via Coursera. No science background is required. The course offers a comprehensive understanding of mRNA medicines, how they work, and their potential applications. For $APDN investors, you will gain insight into the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, and autoimmune diseases that LineaRx, Inc., our biotherapeutics subsidiary, can enable. Applied DNA Sciences #mRNA #geneticmedicine

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells. The authors of this new NEJM paper conducted a phase 1–2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. In this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. Chinese Antibody Society is an independent non-profit, non-government global professional organization with focus upon antibody-based therapeutics. Our society’s official journal, Antibody Therapeutics (2023 CiteScore: 8.7), is an international peer-reviewed, open access journal published by Oxford University Press. You are welcome to visit the official website of the journal (see link below) and submit your therapeutic antibody related manuscripts to our journal. https://lnkd.in/gsTu_U2 #antibodies #antibody #antibodytherapeutics #mabs #mab #biologics

🔬 Researchers from Texas Biomedical Research Institute, University of Alabama at Birmingham, and Columbia University have taken a step closer towards the development of universal COVID-19 antibodies! They developed a human monoclonal antibody named 1301B7 with broad specificity for SARS-CoV-2 JN.1 and other variants. As a receptor binding domain antibody, it targets part of the spike protein responsible for enabling the virus to bind and enter a cell. As of now, a provisional invention patent for 1301B7 has been filed and is currently in the process of licensing for commercialization. Read the preprint here 👉 https://lnkd.in/eYYT-EAB #Biointron #Antibodies #Monoclonal #PharmaNews #DrugDevelopment #DrugDiscovery #COVID #Healthcare #Virus #SARSCoV2 #Therapeutic

I'm happy to share my final first-author paper from my postdoctoral fellowship published today in Science Translational Medicine. In collaboration with Gilead Sciences, we tested an oral antiviral drug candidate that broadly targets an Achilles heel on human and zoonotic coronaviruses. This Achilles heel is the viral polymerase, which is a viral protein required for the virus to make copies of itself once inside host cells. This viral protein is highly conserved among many distinct animal and human coronaviruses and is a rational target for broad spectrum antiviral drugs. This orally administered drug candidate had strong therapeutic and broad spectrum efficacy in mice infected with SARS-CoV-1 2003, SARS-CoV-2 including highly mutated variants, MERS-CoV, a myriad of zoonotic origin coronaviruses from bats, and human coronaviruses that cause the common cold. This oral antiviral broad spectrum drug is similar to Paxlovid in that, theoretically, could be taken at the comfort of your home while coronavirus disease symptoms resolve to prevent viral transmission in community settings. This broad spectrum oral drug represents a tool in our growing armamentarium of antivirals for #pandemicpreparedness for future, emerging and re-emerging coronaviruses that may infect humans. The mode of action of this drug is different from the mode of vaccines so this oral drug provides a potential future alternative treatment strategy to mitigate the spread and disease caused by coronaviruses that have yet to emerge. This work was a key part of the #AViDD center funded at University of North Carolina at Chapel Hill by the The National Institutes of Health https://lnkd.in/erppebC3

We are highlighting a series of popular and impactful articles published in 2024 in our journal, Antibody Therapeutics (2022 CiteScore: 6.4). The title of the 5th article we’d like to feature is “Fc gamma receptors promote antibody-induced LILRB4 internalization and immune regulation of monocytic AML” contributed by Zhiqiang An from The University of Texas Health Science Center at Houston (UTHealth Houston) . The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40–60%. Here researchers defined a FcγR-dependent antigenic modulation mechanism underlying the function of an immunoreceptor blocking antibody for the first time in myeloid malignancy. This research also facilitated the development of safe, precision-targeted antibody therapeutics in myeloid malignancies with greater potency and efficacy. https://lnkd.in/eZ_GbzSp Antibody Therapeutics (2022 CiteScore: 6.4) is the official journal of Chinese Antibody Society (CAS), a non-profit, non-government global professional organization with focus upon antibody-based therapeutics. CAS’s 2024 Annual Conference will take place in Cambridge, MA, USA, on Saturday, May 11, 2024. The theme of this conference is “Beyond Borders: Advancements in Antibody-Based Therapeutics in Uncharted Territories". You are welcome to register for the conference right NOW via the following link. https://lnkd.in/ecmFPA4v   #biologics #antibody #antibodies #antibodydiscovery #antibodytherapeutics #mab #mabs #annualmeeting #annualconference

Monoclonal Antibody vs Polyclonal Antibody in Biomedical Research Both monoclonal and polyclonal antibodies are indispensable tools in biomedical research, but they differ greatly in their production, specificity, and applications. Monoclonal antibodies (mAbs) are produced by identical immune cells cloned from a single parent cell, making them highly specific for a single epitope on an antigen. This specificity allows for precise targeting in research, diagnostic, and therapeutic applications. In biomedical research, mAbs are particularly valuable in techniques such as western blots, immunohistochemistry (IHC), and flow cytometry, where detection of a specific protein or antigen is critical. Their consistency across experiments makes mAbs a top choice for applications that require reproducibility and accuracy. Polyclonal antibodies (pAbs), on the other hand, are produced from multiple B cell clones, resulting in a mixture of antibodies that recognize multiple epitopes on the same antigen. This diversity is extremely useful in studies that require reliable detection of a target, such as in immunoprecipitation, enzyme-linked immunosorbent assays (ELISAs), and certain diagnostic tests. pAbs are able to bind to multiple epitopes, which increases the possibility of antigen detection even when some epitopes are masked or altered, making them more flexible in detecting antigens in different contexts. However, due to the polyclonal nature of pAbs, batch-to-batch variability can lead to inconsistent experimental results. In contrast, mAbs are consistent and better suited for applications that require precise quantitation and minimal cross-reactivity. In summary, monoclonal antibodies offer unparalleled specificity and consistency, while polyclonal antibodies offer robustness and versatility. The choice between mAbs and pAbs depends on the specific requirements of the study, with each type offering different advantages. References [1] Neil Lipman et al., ILAR J 2005 (10.1093/ilar.46.3.258) [2] Michele Busby et al., Epigenetics Chromatin 2016 (10.1186/s13072-016-0100-6) [3] Anchal Singh et al., Animal Biotechnology 2020 (https://lnkd.in/dYZG47t2) #MonoclonalAntibodies #PolyclonalAntibodies #BiomedicalResearch #Immunology #Diagnostics #AntibodyApplications #LabTools

https://lnkd.in/g7Js3FDp At last, peer-reviewed validation of what I've been saying since 2021 when I experienced 9 months of whole-body inflammation following administration of the Moderna mRNA COVID-19 vaccine, leading to extreme fatigue and cognitive dysfunction. "Several studies have utilized a lipid nanoparticle delivery system to enhance the effectiveness of mRNA therapeutics and vaccines. However, these nanoparticles are recognized as foreign materials by the body and stimulate innate immunity, which in turn impacts adaptive immunity. Therefore, it is crucial to understand the specific type of innate immune response triggered by lipid nanoparticles."

In a paper newly published in mAbs, Dragonfly Therapeutics, Inc. and Northeastern University Prof. Zhaohui Sunny Zhou reveal insights into the unique mechanism by which agonistic antibody 2D3 binds NKG2D, a key activating receptor expressed on NK cells and subsets of T cells. From the abstract: Natural killer (NK) cells are effector cells of the innate immune system that distinguish between healthy and abnormal cells through activating and inhibitory receptor signaling. NKG2D, a homodimeric activating receptor expressed on NK cells, recognizes a diverse class of stress ligands expressed by cells experiencing infection, malignant transformation, chronic inflammation, and other cellular stresses. Despite the variety of NKG2D ligands, they all bind the receptor asymmetrically in a 1:1 ligand to homodimeric NKG2D stoichiometry. In contrast, as we report herein, the agonistic antibody 2D3 binds NKG2D with a 2:1 stoichiometry of its antigen binding fragments to homodimeric NKG2D and a largely distinct epitope. This binding interaction, as compared to NKG2D natural ligands, suggests there may be unique mechanisms to engage this receptor while offering possible benefits when incorporated into an IgG-based therapeutic. https://lnkd.in/edwu9CWm