Rech Andrew J, Vonderheide Robert H
Abramson Family Cancer Research Institute and the University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Ann N Y Acad Sci. 2009 Sep;1174:99-106. doi: 10.1111/j.1749-6632.2009.04939.x.
CD4(+) regulatory T cells frustrate productive tumor immune surveillance and represent an obstacle for cancer immunotherapy. In mice, anti-CD25 antibody is an effective method of depleting CD25(+) FOXP3(+) T regulatory cells (Tregs) in vivo and enhancing cancer immunity. Here, we propose the use of the anti-CD25 monoclonal antibody daclizumab for the depletion of Tregs in cancer patients. In early results from an ongoing clinical trial, a single intravenous infusion of daclizumab in patients with metastatic breast cancer is associated with a marked and prolonged elimination of CD25(+) FOXP3(+) Tregs in peripheral blood. When a cancer antigen peptide vaccine is administered during the daclizumab-induced Treg nadir, effective generation of cytotoxic T lymphocytes has been observed, including those specific for neo-antigens, such as cytomegalovirus peptide used as an immunological control. If confirmed in additional patients, these observations suggest that daclizumab may be an effective and available therapeutic agent for Treg modulation in patients with cancer.
CD4(+)调节性T细胞会阻碍有效的肿瘤免疫监视，是癌症免疫治疗的一个障碍。在小鼠中，抗CD25抗体是一种在体内耗竭CD25(+)FOXP3(+)调节性T细胞（Tregs）并增强癌症免疫力的有效方法。在此，我们提议使用抗CD25单克隆抗体达利珠单抗来耗竭癌症患者体内的Tregs。在一项正在进行的临床试验的早期结果中，转移性乳腺癌患者单次静脉输注达利珠单抗与外周血中CD25(+)FOXP3(+)Tregs的显著且持久清除有关。当在达利珠单抗诱导的Treg最低点期间给予癌症抗原肽疫苗时，已观察到细胞毒性T淋巴细胞的有效生成，包括对新抗原特异的细胞毒性T淋巴细胞，如用作免疫对照的巨细胞病毒肽。如果在更多患者中得到证实，这些观察结果表明达利珠单抗可能是一种对癌症患者进行Treg调节的有效且可用的治疗药物。
