Directed Evolution of Therapeutic Antibodies Targeting Glycosylation in Cancer.

ABSTRACT: Glycosylation patterns commonly change in cancer, resulting in expression of tumor-associated carbohydrate antigens (TACA). While promising, currently available anti-glycan antibodies are not useful for clinical cancer therapy. Here, we show that potent anti-glycan antibodies can be engineered to acquire cancer therapeutic efficacy. We designed yeast surface display to generate and select for therapeutic antibodies against the TACA SLe^a (CA19-9) in colon and pancreatic cancers. Elite clones showed increased affinity, better specificity, improved binding of human pancreatic and colon cancer cell lines, and increased complement-dependent therapeutic efficacy. Molecular modeling explained the structural basis for improved antibody functionality at the molecular level. These new too

SUBMITTER: Amon R 

PROVIDER: S-EPMC7601599 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature