MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

An affinity threshold for maximum efficacy in anti-PD-1 immunotherapy

Author(s)
Cowles, Sarah C.; Sheen, Allison; Santollani, Luciano; Lutz, Emi A.; Lax, Brianna M.; Palmeri, Joseph R.; Freeman, Gordon J.; Wittrup, K. Dane; ... Show more Show less
Thumbnail
DownloadKMAB-2022-0057R1_Wittrup_edited (1).pdf (3.347Mb)
Open Access Policy

Open Access Policy

Creative Commons Attribution-Noncommercial-Share Alike

Additional downloads
Manuscript and supplemental files (16.83Mb)
Open Access Policy

Open Access Policy

Creative Commons Attribution-Noncommercial-Share Alike

Terms of use
Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
Metadata
Show full item record
Abstract
Monoclonal antibodies targeted to the programmed cell death protein 1 (PD-1) remain the most prevalent cancer immunotherapy both as a monotherapy and in combination with additional therapies. Despite the extensive success of anti-PD-1 monoclonal antibodies in the clinic, the experimental relationship between binding affinity and functional potency for anti-PD-1 antibodies in vivo has not been reported. Anti-PD-1 antibodies with higher and lower affinity than the nivolumab or pembrolizumab are entering the clinic and show varied preclinical efficacy. Here, we explore the role of broad-ranging affinity variation within a single lineage in a syngeneic immunocompetent mouse model. By developing a panel of murine anti-PD-1 antibodies with varying affinity (ranging from KD = 20 pM - 15 nM), we find that there is a threshold affinity required for maximum efficacy at a given dose in the treatment of the MC38 adenocarcinoma model with anti-PD-1 immunotherapy. Physiologically based pharmacokinetic modeling complements interpretation of the experimental results and highlights the direct relationship between dose, affinity, and PD-1 target saturation in the tumor.
Date issued
2022-08-04
URI
https://hdl.handle.net/1721.1/144276
Department
Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Biological Engineering
Journal
mAbs
Publisher
Taylor & Francis
Citation
Cowles, Sarah C., Sheen, Allison, Santollani, Luciano, Lutz, Emi A., Lax, Brianna M. et al. 2022. "An affinity threshold for maximum efficacy in anti-PD-1 immunotherapy." mAbs, 14 (1).
Version: Author's final manuscript
ISSN
1942-0862
1942-0870

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.