Establishment of a system that allows selective
drug delivery and gene silencing to a
tumor is expected to enable targeted
therapy. We constructed a genetically modified adenovirus incorporating an
IgG Fc-binding motif from the Staphylococcus
protein A, Z33 (Adv-FZ33). By cross-linking the Adv-FZ33 virus and the
surface antigen molecules with the targeting
monoclonal antibodies (mAbs), we attained highly enhanced gene deliveries into the respective
antigen-positive
cancer cells. Therefore, we aimed to establish a systematic screening method to search for antibody and cell surface target candidates that would provide highly selective anti-
cancer reagents to malignant
tumors. Using an Adv-FZ33, hybridoma libraries producing a variety of mAbs for human pancreatic, prostate, lung or ovarian
carcinoma cells were screened, and we were able to selectively obtain several mAbs which had potent high affinity and recognized
antigens of high structure. Within these mAbs, we have identified
tumor cell target molecules including not only
carcinoembryonic antigen (CEA),
epithelial cell adhesion molecule (
EpCAM),
epidermal growth factor receptor (EGFR), prostate specific membrane
antigen (PSMA) but also novel
tumor surface target molecules such as
phosphatidic acid phosphatase type 2a (PAP2a) and
interleukin-13 receptor variant α2 (IL-13Rα2) as
tumor antigens. Overall, these results indicate that this type of inductive method approach is a reliable strategy for screening in antibody
therapy on par with antibody-dependent drug-delivery system.