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Naoyuki Okabe
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-23 - Delta-Like 1 Homolog (DLK1) Expression in Non-Small-Cell Lung Cancer and the Development of Radioimmunotherapy Targeting DLK1 (ID 713)
09:45 - 18:00 | Author(s): Naoyuki Okabe
- Abstract
Background
Currently, treatments for advanced non-small-cell lung cancer (NSCLC) have progressed with the development of molecular targeted drugs and immune checkpoint inhibitors. However, most tumors have become resistant to these treatments. In small cell lung cancer (SCLC), the Notch receptor ligand family, which regulates cell proliferation, is expected to be a therapeutic target. Among this family, Rovalpituzumab is an antibody-drug conjugate directed against Delta-like ligand 3 (DLL3) and showed promising effects in phase 1 trials. However, in NSCLC, clinical impact of this Notch ligand family is still unknown. We therefore focused on Delta-like 1 homolog (DLK1), a noncanonical Notch ligand, which is not also yet fully understood in lung cancer.
Method
We assessed the correlation between clinical features and DLK1 expression in resected specimens from 101 NSCLC patients who had undergone complete resection in the Fukushima Medical University Hospital between January 2012 and January 2017, and were available for analysis. We assessed DLK1 expression on tumor cells using immunohistochemistry with anti-DLK1 antibody (clone DI-2-20, IgG1). Moreover, cell and animal experiments were performed for the development of radioimmunotherapy using this anti-DLK1 antibody.
Result
In 101 patients with NSCLC, 17 (16.8%) had DLK1 positive tumors. There was no association between DLK1 expression and pathological staging. DLK1 expression was associated with recurrence-free survival (p<0.01) but not overall survival. In addition, iodine-125 labeled anti-DLK1 antibody (HuBA-13D) was specifically incorporated into DLK1 on the tumor cell membrane in cell lines of human SCLC and human neuroblastoma. Furthermore, the complex was specifically incorporated into tumor tissue in a mouse model with human neuroblastoma.
Conclusion
The results of the present study indicate that DLK1 expression could be a promising prognostic factor for recurrence in patients with resected NSCLC. In addition, DLK1 could be a therapeutic target for radioimmunotherapy for NSCLC by using our DLK-1 antibody.
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P2.06 - Mesothelioma (ID 170)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.06-20 - Characterization of Claudin15 as a New Diagnostic Marker for Malignant Pleural Mesotheliomas (ID 1770)
10:15 - 18:15 | Author(s): Naoyuki Okabe
- Abstract
Background
Malignant pleural mesotheliomas (MPMs) is a fatal disease mainly caused by past exposure to asbestos. MPMs are classified into three main histological subtypes: epithelioid, sarcomatoid, and biphasic type. There have been known several immunopathological markers for diagnosing MPMs, but there are not enough reliable markers, which often makes it difficult to diagnose MPMs correctly. In the present study, we investigated whether Claudin15 serves as a diagnostic and therapeutic target for MPMs. Claudins are four-transmembrane proteins and form a protein family consisting 27 members in humans. Specific combination of claudins are differentially expressed in different organs and form tight junctions with different permeability. Expression of Claudin15 has been known to be increased at mRNA level in MPMs.
Method
Since 2003 to 2018, 34 patients were diagnosed with MPMs in our hospital. We made a new anti-Claudin15 rat monoclonal antibody, and established a hybridoma clone suitable for IHC. We immunostained 34 tissues with newly established anti-Claudin15 antibody, and compared the staining intensity and occupation with those of Calretinin, a known marker for MPMs. We also immunostained poorly differentiated lung adenocarcinomas, which are sometimes hardly distinguishable with MPMs, with anti-Claudin15 antibody to examine whether Claudin15 staining can distinguish MPMs from adenocarcinomas.
Result
Of the 34 cases, the epithelial type was 27 cases, the sarcomatoid type was 1 case, and the biphasic type was 6 cases. The overall expression rate was 53% for Claudin15 and 59% for Calretinin. In terms of histology type, Claudin15 was 50% and Calretinin was 65% in the epithelial type, while Claudin15 was 80% and Calretinin was 40% in the biphasic type. There was only one sarcomatoid type, neither was expressed. Poorly differentiated adenocarcinomas showed no or very low-level expression of Claudin15.
Conclusion
Our results suggest that Claudin15 could be a novel diagnostic marker for MPMs, especially for biphasic type. Greater number of cases and further analyses would be required to establish Claudin15 as a diagnostic impact for MPMs in clinical use.
