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Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria

Nature Communications. 2024-03; 
Stian Foss?,?Siri A Sakya,?Leire Aguinagalde,?Marta Lustig,?Jutamas Shaughnessy,?Ana Rita Cruz?,?Lisette Scheepmaker,?Line Mathiesen,?Fulgencio Ruso-Julve,?Aina Karen Anthi,?Torleif Tollefsrud Gj?lberg
Products/Services Used Details Operation
Gene Synthesis Expression vectors encoding the heavy chain (HC) and light chain (LC) of NIP64, anti-CD20 (mAb2, mAb1, mAb9 and ofatumumab)42,65, anti-S. aureus?WTA (4497)46, anti-S. pneumonia?(Dob1)48?and anti-N. gonorrhoeae?(2C7)66?specific mouse-human chimeric or human WT IgG variants were generated by synthesizing cDNA followed by subcloning into the described pLNOH2/pLNOk vector system (Genscript Inc). Get A Quote

摘要

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-posi... More

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