Effects of Maackia amurensis seed lectin (MASL) on OSCC cell morphology, PDPN expression, growth, and motility in a phase 1 clinical trial

BACKGROUND: Podoplanin (PDPN) has emerged as a functionally relevant biomarker and chemotherapeutic target expressed by OSCC cells. PDPN signaling can directly increase tumor cell invasion and metastasis, and also inhibit host lymphocyte activation and immune response. Accordingly, antibodies and Maackia amurensis seed lectin (MASL) can target the PDPN receptor to inhibit OSCC cell migration and viability. However, the effects of MASL on OSCC cells in oral cancer patients has not yet been reported. METHODS: We conducted a Phase 1 human clinical trial to examine the effects of a single 100 mg oral dose of MASL on OSCC cell morphology, PDPN expression, and immune cell infiltration in lesions in oral cancer patients. We also examined the effects of MASL on the PDPN expression, motility, and viability of cells cultured from these patient lesions. In addition, we examined the ability of antibodies to target PDPN and kill OSCC cells by near-infrared photoimmunotherapy. RESULTS: MASL administration was found to be safe and did not produce any adverse effects in any patients. While this single dose did not affect OSCC cell morphology in lesions in situ, it did appear to increase lymphocyte infiltration into tumor fields in one patient by over 5 fold (p < 0.01). In addition, MASL inhibited the growth and motility of all OSCC cells cultured from these patient lesions in a dose responsive manner in vitro (p < 0.05 in all cases) We also report that antibodies can target PDPN on OSCC cells obtained from these patients to destroy them by near-infrared photoimmunotherapy (NIR-PIT). CONCLUSION: These results suggest that protocols using MASL and photoimmunotherapies that target PDPN can be developed to effectively treat OSCC lesions in oral cancer patients.