ARTICLE | Translation in Brief

Miniaturizing immunotherapy

A small protein antagonist of the PD-1 pathway is more effective than antibodies

October 1, 2015 7:00 AM UTC

A Stanford University team has engineered a small protein antagonist of the PD-1 pathway that could compete with the panoply of antibodies in development or on the market because it can penetrate tumors better. Newco Ab Initio Biotherapeutics Inc. has licensed the compound from Stanford, but will likely need to address the risk that the large number of amino acid changes in the engineered protein could create immunogenicity problems in the clinic.

The antagonist is a variant of the programmed cell death 1 (PD-1; PDCD1; CD279) extracellular domain that binds PD-1 ligand 1 (PD-L1; B7-H1; CD274) on tumors with more than 30,000-fold higher affinity than the wild-type protein...