Generation of an anti-desmoglein 3 antibody without pathogenic activity of pemphigus vulgaris for therapeutic application to squamous cell carcinoma.

ABSTRACT: It is ideal for the target antigen of a cytotoxic therapeutic antibody against cancer to be cancer-specific, but such antigens are rare. Thus an alternative strategy for target selection is necessary. Desmoglein 3 (DSG3) is highly expressed in lung squamous cell carcinoma, while it is well-known that anti-DSG3 antibodies cause pemphigus vulgaris, an autoimmune disease. We evaluated DSG3 as a novel target by selecting an epitope that exerts efficacy against cancer with no pathogenic effects in normal tissues. Pathogenic anti-DSG3 antibodies induce skin blisters by inhibiting the cell-cell interaction in a Ca2+-dependent manner. We screened anti-DSG3 antibodies that bind DGS3 independent of Ca2+ and have high antibody-dependent cell cytotoxicity (ADCC) activity against DSG3-expressing cells.

SUBMITTER: Funahashi SI 

PROVIDER: S-EPMC6267343 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature