Nature communications, 2024-03, Vol.15 (1), p.2007-2007, Article 2007
- Foss, Stian
- Sakya, Siri A.
- Aguinagalde, Leire
- Lustig, Marta
- Shaughnessy, Jutamas
- Cruz, Ana Rita
- Scheepmaker, Lisette
- Mathiesen, Line
- Ruso-Julve, Fulgencio
- Anthi, Aina Karen
- Gjølberg, Torleif Tollefsrud
- Mester, Simone
- Bern, Malin
- Evers, Mitchell
- Bratlie, Diane B.
- Michaelsen, Terje E.
- Schlothauer, Tilman
- Sok, Devin
- Bhattacharya, Jayanta
- Leusen, Jeanette
- Valerius, Thomas
- Ram, Sanjay
- Rooijakkers, Suzan H. M.
- Sandlie, Inger
- Andersen, Jan Terje
2024
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- Autor(en) / Beteiligte
- Foss, Stian
- Sakya, Siri A.
- Aguinagalde, Leire
- Lustig, Marta
- Shaughnessy, Jutamas
- Cruz, Ana Rita
- Scheepmaker, Lisette
- Mathiesen, Line
- Ruso-Julve, Fulgencio
- Anthi, Aina Karen
- Gjølberg, Torleif Tollefsrud
- Mester, Simone
- Bern, Malin
- Evers, Mitchell
- Bratlie, Diane B.
- Michaelsen, Terje E.
- Schlothauer, Tilman
- Sok, Devin
- Bhattacharya, Jayanta
- Leusen, Jeanette
- Valerius, Thomas
- Ram, Sanjay
- Rooijakkers, Suzan H. M.
- Sandlie, Inger
- Andersen, Jan Terje
- Titel
- Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria
- Ist Teil von
- Nature communications, 2024-03, Vol.15 (1), p.2007-2007, Article 2007
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2024
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions. Antibody based biologics are a rapidly growing class of therapeutics with interest to enhance their performance, distribution, longevity and effectivity. Here, authors report the engineering of human IgG Fc to enhance plasma half-life, mucosal distribution and killing of cancer cells and bacteria.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-024-46321-9Titel-ID: cdi_doaj_primary_oai_doaj_org_article_e2bf31ade1774fb9ab1a7bfa70490845
- Format
- –
- Schlagworte
- 13/109, 631/250/2152/2153/1291, 631/250/2501, 631/250/251, 631/250/2520, 64/110, 64/60, 82/1, 82/103, 82/16, 82/29, 82/80, 82/83, Amino acids, Animals, Anti-Bacterial Agents - therapeutic use, Antibodies, Antibodies, Monoclonal, Bacteria, Cancer, Complement system, Gram-negative bacteria, Gram-Negative Bacteria - metabolism, Gram-positive bacteria, Gram-Positive Bacteria - metabolism, Half-Life, Histocompatibility Antigens Class I - metabolism, Humanities and Social Sciences, Humans, Immunoglobulin G, Mice, Mice, Transgenic, Monoclonal antibodies, Mucosa, multidisciplinary, Neoplasms - drug therapy, Neoplasms - therapy, Plasma, Receptors, Fc, Science, Science (multidisciplinary), Therapeutic applications, Transgenic mice