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A Genetic Approach to Display and Dissect the Cancer‐Associated O‐Glycoepitome
Author(s) -
Clausen Henrik
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.00094
Subject(s) - epitope , glycan , monoclonal antibody , glycoprotein , glycosylation , antibody , mucin , antigen , biology , glycopeptide , microbiology and biotechnology , chemistry , computational biology , biochemistry , immunology , antibiotics
A hallmark of cancer is aberrant protein O‐glycosylation with expression of truncated immature O‐glycans including the classical Tn, STn, and T pancarcinoma antigens. The truncation of O‐glycans not only present epitopes recognized by the natural low affinity antibodies to the TTn glycan haptens, which are the basis for the polyagglutination phenomena, but also expose composite aberrant O‐glycopeptide epitopes that are not normally expressed and can elicit high affinity IgG antibodies. Several examples of monoclonal antibodies with high selectivity for truncated O‐glycopeptide epitopes, which in effect selectively target the cancer form of O‐glycoproteins, have been produced in the past. Studies demonstrate that such epitopes serve as highly cancer‐specific targets potentially amenable for potent T‐cell engaging strategies, however, the current insight into the abundance and distribution of aberrant O‐glycopeptide epitopes and the optimal glycoforms for these remain limited. To systematically explore antibody epitopes available in the cancer‐associated O‐glycoproteome, we have developed a cell‐based platform for display and production of human O‐glycoproteins with homogeneous truncated glycoforms. This platform includes CHO and HEK293 cells stably engineered with homogeneous glycosylation capacities for the Tn, STn, and T glycoforms, and a panel of reporter expression constructs containing segments of human mucins and mucin‐like domains from O‐glycoproteins for display of these with different O‐glycans. An overview of these efforts will be presented.