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Iwao Shimomura



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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-34 - Inhibition of the HGF/c-Met Pathway for Malignant  Mesothelioma with an Intra-Thoracic Injection of the NK4 Expressing Adenoviral Vectors (ID 11796)

      16:45 - 18:00  |  Author(s): Iwao Shimomura

      • Abstract

      Background

      The HGF/c-Met pathway is up-regulated in human mesothelioma. In a preclinical study, the HGF/c-Met suppression with NK4, homologous to HGF, produced anti-tumor effects to mesothelioma cells. Mesothelioma grows in a thoracic cavity and the distant metastasis to extra-thoracic organs is infrequent which is suitable for local treatment including gene therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a phase 1 clinical trial of gene therapy using the NK4 gene-expressing adenoviruses (Ad-NK4) to control the intra-thoracic local tumor growth. We injected Ad-NK4 into the intra-thoracic cavity once with a dose escalation manner from 1010 to 1012 virus particles per patient and to examine safety and efficacy for a month after the administration.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 11 patients compatible with the inclusion criteria entered into the study (Low dose 3, Mediumu dose 3, High dose 5). Most frequent occurred adverse event was Grade 1 transient fever after injection. Severe adverse effects (Grade3 or 4) or treatment-related death were not found, and 3 long survivor were currently followed up. Tumor shrinkages were not observed and response to therapy were SD at best. Antibody to adenovirus was observed in most cases that lasting longer than 30-days. An investigation on a gene transduction level is now on-going.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Direct injection of Ad-NK4 vectors into the pleural cavity, up to the dose of 1012 v,p is safe. Combination ANK4 gene therapy with chemotherapy or immunotherapy may be feasible.

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