期刊
JOURNAL OF IMMUNOTHERAPY
卷 33, 期 3, 页码 316-325出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e3181c1f216
关键词
melanoma; etaracizumab; pharmacodynamic; alpha(v)beta(3); FAK
资金
- MedImmune, LLC
AlphaVbeta3 (alpha(v)beta(3)) is an important molecule for tumor-induced angiogenesis and is upregulated in metastatic melanoma (MM). We proposed to study the mechanism of action of etaracizumab, a monoclonal antibody targeting alpha(v)beta(3), in MM. Patients with MM and biopsiable tumor were treated with etaracizumab in 3 dose cohorts starting from 8 mg/kg. Tumor saturation by etaracizumab using LM609 immunohistochemical staining of tumor sections was the primary endpoint. Subsequent dose cohorts were defined based on the tumor saturation by etaracizumab. Secondary end points were analysis of clinical benefit and changes from baseline of several tumor and peripheral blood biomarkers. Eighteen patients were enrolled at 3 dose levels. Etaracizumab showed better melanoma cell saturation at the 8 mg/kg and 1 mg/kg dose compared with the 4 mg/kg dose and better vascular endothelial cell saturation at 8 mg/kg compared with lower dose groups. Etaracizumab demonstrated an acceptable safety profile. The optimal biologic dose out of those selected for investigation was 8 mg/kg. Patients treated at the highest dose may have had better clinical benefit secondary to suppression of the activated immediate downstream effector of alpha(v)beta(3) signaling, FAK, in melanoma cells, but this alone did not ultimately affect melanoma cell proliferation or apoptosis. No apparent antiangiogenic or immunomodulatory effects of etaracizumab were noted.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据