Enhanced antibody half-life improves in vivo activity

By J. Zalevsky, A. K. Chamberlain, H. Horton, S. Karki, Irene Leung, T. Sproule, G. A. Lazar, D. Roopenian, J. Desjarlais. Nature Biotechnology, 2010

644 citations recorded by the source corpus.

Improved affinity for the neonatal Fc receptor (FcRn) is known to extend antibody half-life in vivo. However, this has never been linked with enhanced therapeutic efficacy. We tested whether antibodies with half-lives extended up to fivefold in human (h)FcRn transgenic mice and threefold in cynomolgus monkeys retain efficacy at longer dosing intervals. We observed that prolonged exposure due to FcRn-mediated enhancement of half-life improved antitumor activity of Fc-engineered antibodies in an hFcRn/Rag1−/− mouse model. This bridges the demand for dosing convenience with the clinical necessity of maintaining efficacy.

Subfields: Immunology, Molecular Biology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/66f0151669b199e2b1a32c57e8cd14b41ce548c9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. N. Bertrand
2. P. Carter

In Molecular Biology

1. A. Chan
2. N. Bertrand
3. A. Teplyakov
4. Gary Gilliland
5. Dennis R. Goulet
6. M. Chiu
7. P. Carter
8. J. Leroux

In Radiology, Nuclear Medicine and Imaging

1. A. Chan
2. N. Bertrand
3. A. Teplyakov
4. Gary Gilliland
5. Dennis R. Goulet
6. M. Chiu
7. P. Carter
8. J. Leroux

Citations in the corpus

• Antibody Structure and Function: The Basis for Engineering Therapeutics (2019, background): “developed an IgG1 LS mutant (M428L/N434S) with an 11-fold increased FcRn affinity and 3- to 5-fold increased half-life [439].”
• Therapeutic antibodies for autoimmunity and inflammation (2010, background): “Fc mutations that extend pharmacokinetic half-life can also enhance in vivo efficacy, which has been recently shown for the first tim”
• The journey of a drug-carrier in the body: an anatomo-physiological perspective. (2012, background): “Still, today, PEG remains themost frequently utilized polymer to augment the DH of therapeutic molecules [70,90], but other hydrosoluble polymers [91–93] as well as synthetic linear polypeptides [94,95] have also been employed for this purpose.”