Journal
CANCER SCIENCE
Volume 110, Issue 5, Pages 1653-1664Publisher
WILEY
DOI: 10.1111/cas.13979
Keywords
antibody; malignant mesothelioma; podoplanin; radiation; radioimmunotherapy
Categories
Funding
- KAKENHI [16K10748, 17K07299, 17K10497, 18H02774, 18K07778]
- AMED-CREST [JP18gm0710003]
- Japan Agency for Medical Research and Development [JP18am0101078]
- Grants-in-Aid for Scientific Research [17K10497, 18K07778, 18H02774] Funding Source: KAKEN
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Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is highly expressed in malignant mesothelioma. The rat-human chimeric antibody NZ-12 has high affinity for human podoplanin and antibody-dependent cellular cytotoxicity and is applicable for radioimmunotherapy (RIT) to enhance the antitumor effect. In the present study, we evaluated the invivo and invitro properties of radiolabeled NZ-12 and the antitumor effect of RIT with Y-90-labeled NZ-12 in an NCI-H226 (H226) malignant mesothelioma xenograft mouse model. In-111-labeled NZ-12 bound specifically to H226 cells with high affinity, and accumulation was high in H226 tumors but low in major organs. RIT with Y-90-labeled NZ-12 significantly suppressed tumor growth and prolonged survival without body weight loss and obvious adverse effects. Higher podoplanin expression levels were observed in human mesothelioma specimens, suggesting higher tumor accumulation of Y-90-labeled NZ-12 in patients compared with the H226 tumor xenografts. Our findings suggest that Y-90-labeled NZ-12 is a promising RIT agent as a new therapeutic option for malignant mesothelioma that warrants further clinical studies to evaluate the dosimetry and efficacy in patients.
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