Centaur antibodies: Engineered chimeric equine-human recombinant antibodies.
Autor: | Rosenfeld R; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Alcalay R; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Zvi A; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Ben-David A; Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel., Noy-Porat T; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Chitlaru T; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Epstein E; Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel., Israeli O; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Lazar S; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Caspi N; Veterinary Center for Preclinical Research, Israel Institute for Biological Research, Ness Ziona, Israel., Barnea A; Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel., Dor E; Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel., Chomsky I; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Pitel S; Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel., Makdasi E; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel., Zichel R; Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel., Mazor O; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in immunology [Front Immunol] 2022 Aug 19; Vol. 13, pp. 942317. Date of Electronic Publication: 2022 Aug 19 (Print Publication: 2022). |
DOI: | 10.3389/fimmu.2022.942317 |
Abstrakt: | Hyper-immune antisera from large mammals, in particular horses, are routinely used for life-saving anti-intoxication intervention. While highly efficient, the use of these immunotherapeutics is complicated by possible recipient reactogenicity and limited availability. Accordingly, there is an urgent need for alternative improved next-generation immunotherapies to respond to this issue of high public health priority. Here, we document the development of previously unavailable tools for equine antibody engineering. A novel primer set, EquPD v2020, based on equine V-gene data, was designed for efficient and accurate amplification of rearranged horse antibody V-segments. The primer set served for generation of immune phage display libraries, representing highly diverse V-gene repertoires of horses immunized against botulinum A or B neurotoxins. Highly specific scFv clones were selected and expressed as full-length antibodies, carrying equine V-genes and human Gamma1/Lambda constant genes, to be referred as "Centaur antibodies". Preliminary assessment in a murine model of botulism established their therapeutic potential. The experimental approach detailed in the current report, represents a valuable tool for isolation and engineering of therapeutic equine antibodies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Rosenfeld, Alcalay, Zvi, Ben-David, Noy-Porat, Chitlaru, Epstein, Israeli, Lazar, Caspi, Barnea, Dor, Chomsky, Pitel, Makdasi, Zichel and Mazor.) |
Databáze: | MEDLINE |
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