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结合干细胞移植和PD-1阻断的树突状细胞骨髓瘤的融合接种

Vaccination with Dendritic Cell Myeloma Fusions in Conjunction with Stem Cell Transplantation and PD-1 Blockade
作者:Avigan, D. 作者单位:Beth Israel Medical Center, New York. 加工时间:2014-08-22 信息来源:科技报告(AD ) 索取原文[11 页]
关键词:骨髓瘤;干细胞;T淋巴细胞;疫苗;抗体;细胞(生物)
摘 要:However, patients experience disease relapse from a persistent reservoir of chemotherapy resistant disease. There has been strong interest in developing immunotherapeutic strategies to eradicate  residual disease following autologous transplantation. Our group has developed a  tumor vaccine model whereby dendritic cells are fused with tumor cells. In clinical trials, vaccination with fusion cell results in anti-tumor immune and  disease responses in a subset of patients. However, vaccine efficacy is blunted  by tumor mediated immune suppression and the increased presence of regulatory T cells characteristic of patients with malignancy. An important element  contributing to tumor mediated immune suppression is the PD-1/PDL-1 pathway.  PD-L1 exerts a significant role in promoting T cell tolerance by binding PD-1 on activated T cells and suppressing their capacity to secrete stimulatory  cytokines. We have demonstrated that blockade of this pathway results in  enhanced immune responses to DC/myeloma fusion cells ex vivo. In the proposed study, we will examine toxicity, immunologic effect and clinical efficacy of  CT-011 therapy following stem cell transplantation for patients with myeloma.  These endpoints will then be assessed in patients undergoing combined therapy with the vaccine and antibody.
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