Clinical Use of Anti-CD25 Antibody Daclizumab to Enhance Immune Responses to Tumor Antigen Vaccination by Targeting Regulatory T cells
Clinical Use of Anti-CD25 Antibody Daclizumab to Enhance Immune Responses to Tumor Antigen Vaccination by Targeting Regulatory T cells
复制标题
DOI：
10.1111/j.1749-6632.2009.04939.x
复制
发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Vonderheide, Robert H.
中科院分区：
文献类型：
--
作者：
Rech, Andrew J.;Vonderheide, Robert H.
CD4（+）调节性T细胞阻碍了有效的肿瘤免疫监视，并成为癌症免疫治疗的障碍。在小鼠中，抗CD25抗体是体内清除CD25（+）FOXP3（+）T调节细胞（TCRs）和增强癌症免疫的有效方法。在这里，我们建议使用抗CD25单克隆抗体daclizumab用于消除癌症患者中的T细胞。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daclizumab与外周血中CD25（+）FOXP3（+）T淋巴细胞的显著和长期消除相关。当在达克珠单抗诱导的Treg最低点期间施用癌抗原肽疫苗时，已经观察到细胞毒性T淋巴细胞的有效产生，包括对新抗原特异的那些，例如用作免疫对照的巨细胞病毒肽。如果在其他患者中得到证实，这些观察结果表明达克珠单抗可能是癌症患者中调节Treg的有效且可用的治疗剂。
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.