PO.CT01.02 · 临床试验

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

编号 CT047 展板 7 时间 4/20 09:00–12:00 区域 Section 50 主讲 Gary Goldberg, PhD

分会场 First-in-Human Phase I Clinical Trials

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作者与单位

Ariel C. Yin¹, Cayla J. Holdcraft¹, Tyler J. Hellmig¹, Eamonn J. Brace¹, David I. Suster², Alan J. Shienbaum³, Dylan Roden², Evelyne Kalyousef², Ghayoour Mir², Eugenio Capitle², Soly Baredes², Rabie Shanti², Mika K. Kaneko⁴, Yukinari Kato⁴, Hisataka Kobayashi⁵, Aki Furusawa⁵, Mahnaz Fatahzadeh², Gary S. Goldberg¹

¹Rowan University - School of Osteopathic Medicine, Stratford, NJ,²Rutgers University, Newark, NJ,³Pathology Associates of Northeastern Pennsylvania, Dunmore, PA,⁴Tohoku University Graduate School of Medicine, Sendai, Japan,⁵National Cancer Institute, Bethesda, MD

摘要 Abstract

Oral cancer kills over 180 thousand peoplearound the world each year, and can cause permanent sequelae in survivors. Over90 percent of oral cancers are oral squamous cell carcinomas (OSCC). Thepodoplanin (PDPN) receptor has emerged as a functionally relevant biomarker andchemotherapeutic target expressed by OSCC cells. PDPN signaling can directlyincrease tumor cell invasion and metastasis, and inhibit host lymphocyteactivation and immune response. Antibodies and Maackia amurensis seedlectin (MASL) can target PDPN to inhibit OSCC cell migration and viability. Weconducted a Phase 1 human clinical trial to examine the effects of MASL on OSCCcell morphology, PDPN expression, and immune cell infiltration in oral cancerpatient lesions. We also examined the effects of MASL on motility, viability,and PDPN expression in cells cultured from these patient lesions. Oral MASLadministration was found to be safe and did not produce any adverse effects inany patients in this study. MASL did not affect OSCC cell morphology in lesionsin situ, but appeared to increase lymphocyte infiltration into tumor fields inone out of three patients examined within 24 hours after dosing (p<0.01).MASL also inhibited the growth and motility of all OSCC cells cultured fromthese patient lesions in a dose dependent manner in vitro (p<0.05 in allcases). We also examined the ability of antibodies to target PDPN and kill OSCCcells by near-infrared photoimmunotherapy (NIR-PIT). We found that antibodiescan target PDPN on OSCC cells from patients to destroy them by NIR-PIT. Theseresults suggest that protocols using MASL and photoimmunotherapy targeting PDPNcan be developed to effectively treat OSCC lesions in oral cancer patients. Inparticular, these data support the overall approach of using antibodies thatrecognize human PDPN to target and kill human OSCC cells by NIR-PIT. Thesenovel results support a general and powerful approach to use NIR-PIT to treatoral cancer patients and, by deduction, patients with other cancers thatexpress the PDPN receptor.

利益披露 Disclosure

A. C. Yin, Sentrimed Employment, Stock, Stock Option, ), Travel. C. J. Holdcraft, Sentrimed Employment, Stock, Stock Option, ), Travel. T. J. Hellmig, None.. E. J. Brace, None.. D. I. Suster, None. A. J. Shienbaum, Sentrimed ). D. Roden, None.. E. Kalyousef, None.. G. Mir, None.. E. Capitle, None.. S. Baredes, None.. R. Shanti, None.. M. K. Kaneko, None.. Y. Kato, None.. H. Kobayashi, None.. A. Furusawa, None.. M. Fatahzadeh, None. G. S. Goldberg, Sentrimed g., Board of Directors, non-salaried role), Stock, Stock Option, Other Business Ownership, ), Travel, Patent, Trademark, Copyright. PBLMed Trademark, Copyright, Other Intellectual Property, Other, PBLMed.com. PDPN Central Travel, Trademark, Copyright, Other Intellectual Property, Other, PDPN.info.

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