It is important to note that the levels of Trastuzumab-mediated ADCC in patients with ESCC were significantly impaired in comparison with those in healthy donors (Figure 1B), in line www.selleckchem.com/products/Bosutinib.html with our previous report (Mimura et al, 2005b). Taken together, we confirmed that Trastuzumab- and Cetuximab-mediated ADCC was impaired in patients with ESCC in comparison with those in healthy donors, although HER2-expressing or EGFR-expressing ESCC was killed by Trastuzumab- and Cetuximab-mediated ADCC, respectively. IL-21 enhanced Cetuximab-mediated ADCC activity of PBMCs derived from ESCC patients We next analysed the effect of IL-21 on Cetuximab-mediated ADCC, when PBMCs derived from patients and healthy donors were cultured with IL-21 at indicated doses for 24h.

Representative ADCC data showed that Cetuximab-mediated ADCC activity was significantly enhanced by the addition of IL-21 to PBMCs derived from patients and healthy donors (Figure 2A). Summarised data from patients (n=12) and healthy donors (n=10) clearly showed that IL-21 significantly enhanced Cetuximab-mediated ADCC against high EGFR-expressing KYSE30 and low EGFR-expressing KYSE110 in a dose-dependent manner (Figure 2B). It is noteworthy that Cetuximab-mediated ADCC enhanced by IL-21 in patients was high enough in comparison with that in healthy donors; for example, 75.1��7.3 vs 82.2��8.2%, respectively at an E:T ratio of 40:1 and 10��gml?1 of IL-21 against KYSE30 (Figure 2B), in which the original ADCC levels of patients were significantly impaired in comparison with those of healthy donors (Figure 1A).

Thus, IL-21 could efficiently enhance impaired Cetuximab-mediated ADCC in patients with ESCC. Figure 2 Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells (PBMCs) cultured with IL-21. PBMCs derived from patients (oesophageal squamous cell carcinoma (ESCC)) and healthy donors (healthy) were cultured … IL-21 enhanced Trastuzumab-mediated ADCC activity of PBMCs derived from ESCC patients We further investigated the effect of IL-21 on Trastuzumab-mediated ADCC, when PBMCs derived from patients and healthy donors were cultured with IL-21 at indicated doses for 24h. Representative AV-951 ADCC data indicated that Trastuzumab-mediated ADCC activity was significantly enhanced by the addition of IL-21 to PBMCs derived from patients and healthy donors (Figure 3A). Summarised data from patients (n=8) and healthy donors (n=6) clearly showed that IL-21 could significantly enhance Trastuzumab-mediated ADCC activity against high HER2-expressing TE4 and low HER2-expressing KYSE50 in a dose-dependent manner (Figure 3B).