Biomolecular Recognition of the Glycan Neoantigen CA19-9 by Distinct Antibodies

•CA19-9 is a glycan biomarker of cancer.•Crystal structures of two anti-CA19-9 antibodies were determined in complex with CA19-9.•CA19-9 adopts a preferred low-energy conformation.•Recognition of CA19-9 is mediated by intricate networks of polar interactions.•Structure-based design of one antibody resulted with tenfold increase in affinity to CA19-9.