Successful therapeutic options remain elusive for
pancreatic cancer. The exquisite sensitivity and specificity of humoral and cellular immunity may provide therapeutic approaches if
antigens specific for
pancreatic cancer cells can be identified. Here we characterize SAS1B (ovastacin, ASTL,
astacin-like), a
cancer-oocyte
antigen, as an attractive
immunotoxin target expressed at the surface of human
pancreatic cancer cells, with limited expression among normal tissues. Immunohistochemistry shows that most
pancreatic cancers are SAS1Bpos (68%), while normal pancreatic ductal epithelium is SAS1Bneg.
Pancreatic cancer cell lines developed from patient-derived xenograft models display SAS1B cell surface localization, in addition to cytoplasmic expression, suggesting utility for SAS1B in multiple immunotherapeutic approaches. When
pancreatic cancer cells were treated with an anti-SAS1B
antibody-drug conjugate, significant cell death was observed at 0.01-0.1 μg/mL, while SAS1Bneg human keratinocytes were resistant. Cytotoxicity was correlated with SAS1B cell surface expression; substantial killing was observed for
tumors with low steady state SAS1B expression, suggesting a substantial proportion of SAS1Bpos
tumors can be targeted in this manner. These results demonstrate SAS1B is a surface target in
pancreatic cancer cells capable of binding
monoclonal antibodies, internalization, and delivering cytotoxic
drug payloads, supporting further development of SAS1B as a novel target for
pancreatic cancer.