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  P1.07 - Poster Session with Presenters Present (ID 459)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: SCLC/Neuroendocrine Tumors
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 16912

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    P1.07-033 - Trastuzumab Emtansine (T-DM1) Suppresses the Growth of HER2-Positive Small-Cell Lung Cancer in Preclinical Models (ID 3883)

    14:30 - 14:30  |  Author(s): M. Higashiguchi
    • Abstract
    • Slides

    Background:
    To overcome chemoresistance is indispensable to bring about better prognosis in small-cell lung cancer (SCLC). We have reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. Moreover, HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). However, irinotecan-resistant SCLC cells, e.g. SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we studied the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC.
    
    Methods:
    SBC-3/SN-38 (HER2-positive) or OS2RA (HER2-negative) SCLC cells were inoculated subcutaneously in the flank of six-week-old male nude mice. Tumor size was measured with a caliper two or three times per week. When tumor volume reached about 150-200 mm[3], mice were randomly assigned to three treatment groups. Each group was treated with intravenous injection of T-DM1 15 mg/kg, intraperitoneal injection of trastuzumab 30 mg/kg, or saline as control. To confirm the HER2-specific delivery of T-DM1, in vivo imaging was performed. Namely, several tumor-bearing mice were intravenously administered with fluorescence-labeled T-DM1. Fluorescence images of mice were captured with IVIS® Lumina II system (PerkinElmer).
    
    Results:
    Treatment with T-DM1 significantly suppressed the growth of SBC-3/SN-38 xenografts compared with trastuzumab and saline groups. Histological analysis revealed that T-DM1 remarkably induced apoptosis and inhibited proliferation. Fluorescence-labeled T-DM1 definitely accumulated to the xenografts in a HER2-selective fashion.
    
    Conclusion:
    T-DM1 treatment could be an attractive therapeutic option in trastuzumab-resistant HER2-positive SCLC where trastuzumab cannot induce enough ADCC activity. Delivery of a cytotoxic agent DM1 to the inside of cells via HER2-mediated internalization is expected and crucial to exert antitumor effect in such ADCC-lacking SCLC cells. Figure 1
    
    
    
    

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