Nature Communications (Apr 2022)

The engineered CD80 variant fusion therapeutic davoceticept combines checkpoint antagonism with conditional CD28 costimulation for anti-tumor immunity

  • Mark F. Maurer,
  • Katherine E. Lewis,
  • Joseph L. Kuijper,
  • Dan Ardourel,
  • Chelsea J. Gudgeon,
  • Siddarth Chandrasekaran,
  • Sherri L. Mudri,
  • Kayla N. Kleist,
  • Chris Navas,
  • Martin F. Wolfson,
  • Mark W. Rixon,
  • Ryan Swanson,
  • Stacey R. Dillon,
  • Steven D. Levin,
  • Yengo Raymond Kimbung,
  • Masato Akutsu,
  • Derek T. Logan,
  • Björn Walse,
  • Kristine M. Swiderek,
  • Stanford L. Peng

DOI
https://doi.org/10.1038/s41467-022-29286-5
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 14

Abstract

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CD28 costimulatory signalling can be suppressed by immune checkpoints, such as CTLA-4 and PD-1. Here the authors describe the design of the fusion therapeutic davoceticept (ALPN-202), based on a variant CD80 extracellular domain engineered to bind PD-L1 as well as CD28 and CTLA-4, providing direct T cell costimulation and dual checkpoint inhibition to enable anti-tumor immune responses.