RT Journal Article
SR Electronic
T1 Variable PD-1 glycosylation modulates the activity of immune checkpoint inhibitors
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202302368
DO 10.26508/lsa.202302368
VO 7
IS 3
A1 Chu, Chih-Wei
A1 Čaval, Tomislav
A1 Alisson-Silva, Frederico
A1 Tankasala, Akshaya
A1 Guerrier, Christina
A1 Czerwieniec, Gregg
A1 Läubli, Heinz
A1 Schwarz, Flavio
YR 2024
UL https://www.life-science-alliance.org/content/7/3/e202302368.abstract
AB Monoclonal antibodies targeting the immune checkpoint PD-1 have provided significant clinical benefit across a number of solid tumors, with differences in efficacy and toxicity profiles possibly related to their intrinsic molecular properties. Here, we report that camrelizumab and cemiplimab engage PD-1 through interactions with its fucosylated glycan. Using a combination of protein and cell glycoengineering, we demonstrate that the two antibodies bind preferentially to PD-1 with core fucose at the asparagine N58 residue. We then provide evidence that the concentration of fucosylated PD-1 in the blood of non–small-cell lung cancer patients varies across different stages of disease. This study illustrates how glycoprofiling of surface receptors and related circulating forms can inform the development of differentiated antibodies that discriminate glycosylation variants and achieve enhanced selectivity, and paves the way toward the implementation of personalized therapeutic approaches.