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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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

In: Nature Communications, Vol. 15, No. 1, 2007, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Foss, S, Sakya, SA, Aguinagalde, L, Lustig, M, Shaughnessy, J, Cruz, AR, Scheepmaker, L, Mathiesen, L, Ruso-Julve, F, Anthi, AK, Gjølberg, TT, Mester, S, Bern, M, Evers, M, Bratlie, DB, Michaelsen, TE, Schlothauer, T, Sok, D, Bhattacharya, J, Leusen, J, Valerius, T, Ram, S, Rooijakkers, SHM, Sandlie, I & Andersen, JT 2024, 'Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria', Nature Communications, vol. 15, no. 1, 2007. https://doi.org/10.1038/s41467-024-46321-9

APA

Foss, S., Sakya, S. A., Aguinagalde, L., Lustig, M., Shaughnessy, J., Cruz, A. R., Scheepmaker, L., Mathiesen, L., Ruso-Julve, F., Anthi, A. K., Gjølberg, T. T., Mester, S., Bern, M., Evers, M., Bratlie, D. B., Michaelsen, T. E., Schlothauer, T., Sok, D., Bhattacharya, J., ... Andersen, J. T. (2024). Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria. Nature Communications, 15(1), [2007]. https://doi.org/10.1038/s41467-024-46321-9

Vancouver

Foss S, Sakya SA, Aguinagalde L, Lustig M, Shaughnessy J, Cruz AR et al. Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria. Nature Communications. 2024;15(1). 2007. https://doi.org/10.1038/s41467-024-46321-9

Author

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. / Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria. In: Nature Communications. 2024 ; Vol. 15, No. 1.

Bibtex

@article{ad6ec4b50616442892be04c83d8af83f,

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

abstract = "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.",

author = "Stian Foss and Sakya, {Siri A.} and Leire Aguinagalde and Marta Lustig and Jutamas Shaughnessy and Cruz, {Ana Rita} and Lisette Scheepmaker and Line Mathiesen and Fulgencio Ruso-Julve and Anthi, {Aina Karen} and Gj{\o}lberg, {Torleif Tollefsrud} and Simone Mester and Malin Bern and Mitchell Evers and Bratlie, {Diane B.} and Michaelsen, {Terje E.} and Tilman Schlothauer and Devin Sok and Jayanta Bhattacharya and Jeanette Leusen and Thomas Valerius and Sanjay Ram and Rooijakkers, {Suzan H.M.} and Inger Sandlie and Andersen, {Jan Terje}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

doi = "10.1038/s41467-024-46321-9",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

RIS

TY - JOUR

T1 - Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria

AU - Foss, Stian

AU - Sakya, Siri A.

AU - Aguinagalde, Leire

AU - Lustig, Marta

AU - Shaughnessy, Jutamas

AU - Cruz, Ana Rita

AU - Scheepmaker, Lisette

AU - Mathiesen, Line

AU - Ruso-Julve, Fulgencio

AU - Anthi, Aina Karen

AU - Gjølberg, Torleif Tollefsrud

AU - Mester, Simone

AU - Bern, Malin

AU - Evers, Mitchell

AU - Bratlie, Diane B.

AU - Michaelsen, Terje E.

AU - Schlothauer, Tilman

AU - Sok, Devin

AU - Bhattacharya, Jayanta

AU - Leusen, Jeanette

AU - Valerius, Thomas

AU - Ram, Sanjay

AU - Rooijakkers, Suzan H.M.

AU - Sandlie, Inger

AU - Andersen, Jan Terje

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-024-46321-9

DO - 10.1038/s41467-024-46321-9

M3 - Journal article

C2 - 38453922

AN - SCOPUS:85187155801

VL - 15

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2007

ER -

ID: 390521975

Department of Public Health