| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
We elucidated the mechanisms of escape from trastuzumab-mediated ADCC using esophageal squamous cell carcinoma cell clones. The ADCC assay with purified NK cells showed significantly susceptibility to trastuzumab-mediated ADCC in tumor cell clones. These results indicated that the sensitivity to trastuzumab-mediated ADCC was mainly due to the difference in susceptibility to NK cell-mediated ADCC. Furthermore, the degree of permeabilization induced by PFN and apoptosis induced by the combination of PFN with GrB in tumor cell clones was analyzed. As a result, lower sensitivity for PFN/GrB on tumor clones was related to the reduced trastuzumab-mediated ADCC. In conclusion, lower susceptibility to the perforin-granzyme system is one of the important mechanisms explaining escape from trastuzumab-mediated ADCC.
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