2009 Fiscal Year Final Research Report
Mechanisms of escape from trastuzumab-mediated ADCC in esophageal squamous cell carcinoma.
| Project/Area Number |
20790947
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | University of Yamanashi |
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Principal Investigator |
KAWAGUCHI Yoshihiko University of Yamanashi, 医学部附属病院, 診療助教 (80402048)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 食道扁平上皮癌 / 抗体療法 / trastuzumab / Herceptin / 抗体依存性細胞傷害 |
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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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