PO.CT01.02 · 临床试验
在一项1期临床试验中，Maackia amurensis种子凝集素（MASL）对OSCC细胞形态、PDPN表达、活力和运动性的影响
Effects of Maackia amurensis seed lectin (MASL) on OSCC cell morphology, PDPN expression, viability, and motility in a phase 1 clinical trial
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
口腔癌每年在全世界导致超过18万人死亡，并可在幸存者中造成永久性后遗症。超过90%的口腔癌为口腔鳞状细胞癌（OSCC）。足突蛋白（PDPN）受体已成为OSCC细胞表达的具有功能相关性的生物标志物和化疗靶点。PDPN信号可直接增加肿瘤细胞侵袭和转移，并抑制宿主淋巴细胞活化和免疫应答。抗体和Maackia amurensis种子凝集素（MASL）可靶向PDPN以抑制OSCC细胞迁移和活力。我们开展了一项1期人体临床试验，以检测MASL对口腔癌患者病灶中OSCC细胞形态、PDPN表达和免疫细胞浸润的影响。我们还检测了MASL对从这些患者病灶培养的细胞的运动性、活力和PDPN表达的影响。口服MASL给药被证明是安全的，本研究中未在任何患者中产生任何不良反应。MASL未影响原位病灶中的OSCC细胞形态，但在所检测的3例患者中的1例中，给药后24小时内似乎增加了淋巴细胞向肿瘤区域的浸润（p<0.01）。MASL在体外还以剂量依赖方式抑制所有从这些患者病灶培养的OSCC细胞的生长和运动性（所有病例p<0.05）。我们还检测了抗体通过近红外光免疫疗法（NIR-PIT）靶向PDPN并杀伤OSCC细胞的能力。我们发现抗体可靶向患者OSCC细胞上的PDPN，通过NIR-PIT将其摧毁。这些结果提示，可开发使用MASL和靶向PDPN的光免疫疗法的方案，以有效治疗口腔癌患者的OSCC病灶。特别是，这些数据支持使用识别人PDPN的抗体通过NIR-PIT靶向并杀伤人OSCC细胞的总体方法。这些新颖的结果支持了一种普适而强大的方法，即使用NIR-PIT治疗口腔癌患者，并由此推断可用于治疗其他表达PDPN受体的癌症患者。
查看英文原文 English 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.