Purpose: Podoplanin (PDPN) is involved in cancer malignancy. PDPN is highly expressed in both cancer and normal cells. We aimed to develop cancer-specific anti-PDPN mAbs.
Methods: We immunized mice with PDPN-expressing cancer cells, and produced cancer-specific anti-PDPN monoclonal antibodies (mAbs). We characterized mAbs using flow cytometry (FCM) and immmunohistochemistry (IHC). Anti-tumor activities by a mouse-human chimeric mAb was examined using mouse xenograft models of oral cancer cells. We further investigated the possibility of PDPN as a diagnostic marker of oral cancers.
Results: One of established mAbs, LpMab-23 reacted with PDPN-expressing cancer cells, not with normal cells by FCM and IHC using oral cancers. LpMab-23 recognized a cancer-specific glycopeptide including Thr55/Ser56. chLpMab-23 revealed high ADCC and anti-tumor activities against oral cancers. We further showed that LpMab-23 is a prognostic marker of oral cancer. The Kaplan-Meier curves of the five-year new metastasis-free survival rate (nMFS) were significantly lower in LpMab-23-positive patients than in LpMab-23-negative ones.
Conclusion: LpMab-23 has antitumor activities, and LpMab-23-positive cases could be a useful predictor of poor prognosis for oral cancer.