In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2704-2704
Abstract:
(Background and Aim) Both cetuximab and trastuzumab inhibit growth signal by binding to growth factor receptors, and also have an alternative function regarded as ADCC. In this study, we examined cetuximab-mediated ADCC against EGFR-positive colon cancer cells and trastuzumab-mediated ADCC against HER2-positive gastric cancer cells. Moreover, we investigated the new methods to enhance those ADCC activities. (Materials and Methods) We used human gastric cancer cell lines (MKN1, MKN45) and colon cancer cells (HT-29), cetuximab and trastuzumab as an antibody which potentially had ADCC, and non-specific IgG1 antibody as a control. ADCC was measured by Europium release assay: First, we used peripheral blood mononuclear cells (PBMCs) from healthy volunteers as effector, and we prepared those cancer cell lines combined with those kinds of antibodies as target. Next, we used PBMCs activated by IL-2 instead of normal PBMCs. At same time, CD16, perforin, granzyneB on PBMCs were evaluated by Flow Cytometer and PCR. NK activity of PBMN and activated PBMC against for K562 cell and ADCC activity of PBMN and activated PBMC were evaluated. (Results) Cetuximab and trastuzumab didn't kill cancer cells by themselves, but the cytotoxicity of PBMCs was increased when the target cells were treated with these antibodies in advance. This increase was further strengthened by activated PBMCs with IL-2. But IL-2 didn't enhance CD16 expression on PBMCs. Finally PBMC, which have high potential of NK activity shows high ADCC activity, (Conclusion) These two antibody therapy shows ADCC in vitro, As a next step, we have to start in vivo study Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2704. doi:10.1158/1538-7445.AM2011-2704
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-2704
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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