itemprop=description content=Researchers introduced and characterized a novel platform based on monoclonal antibodies (mAbs).
By Neha MathurOct 6 2023Reviewed by Lily Ramsey, LLM In a recent article published in the Journal of Alzheimer’s & Dementia, researchers introduced and characterized a novel platform based on monoclonal antibodies .
Specifically, these mAbs were designed to inhibit the interaction between ApoE and HSPGs, using recombinant constructs of the HSPG domain of ApoE3 and ApoE3Ch. The researchers also investigated whether these mAbs competed for heparin binding to reduce ApoE-derived cytotoxicity in vitro and tau phosphorylation in vivo.
The researchers synthesized peptides corresponding to the N-terminal HSPG-binding region of wild-type and Ch variants of the ApoE3 gene. These peptides induced an immune response in mice, leading to the generation of hybridoma cell lines secreting highly specific anti-ApoE antibodies. Using enzyme-linked immunosorbent assay , the researchers screened supernatants from these hybridoma clones, ultimately identifying 7C11.mAb and 1H4.mAb as the most promising antibodies.
Related StoriesBiologics assays confirmed that 7C11 had the highest binding affinity for ApoE4. In vitro experiments showed that 7C11 effectively reduced ApoE4-HSPG binding, mitigating cytotoxicity, while introducing the Ch mutation on ApoE4 abolished cytotoxicity. Importantly, none of the mAbs bound to mouse ApoE, highlighting their specificity for human ApoE. However, this specificity also posed challenges in assessing their preclinical efficacy in mouse models.
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