Established B16 tumors are rejected following treatment with GM-CSF-secreting tumor cell immunotherapy in combination with anti-4-1BB mAb
Established B16 tumors are rejected following treatment with GM-CSF-secreting tumor cell immunotherapy in combination with anti-4-1BB mAb
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DOI：
10.1016/j.clim.2007.07.005
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发表时间：
2007-10-01
影响因子：
8.6
通讯作者：
Jooss, Karin
中科院分区：
文献类型：
--
作者：
Li, Betty;Lin, Jianmin;Jooss, Karin
在临床和临床前环境中，用经辐照的肿瘤细胞进行免疫以分泌粒细胞-巨噬细胞集落刺激因子（GM-CSF）刺激有效的、特异性的和持久的抗肿瘤免疫。正在评估进一步提高免疫调节剂免疫治疗疗效的努力。基于4-1BB（CD 137）的免疫调节特性，已经假定激动性4-1BB抗体可以为分泌GM-CSF的肿瘤细胞免疫疗法增加额外的抗肿瘤功效。分泌GM-CSF的肿瘤细胞免疫疗法和抗4-1BB单克隆抗体（mAb）治疗的组合导致在B16黑色素瘤模型中建立的肿瘤的排斥。这些抗肿瘤作用与持续的肿瘤特异性CD 8（+）T细胞应答相关。此外，在联合治疗的小鼠中发现功能性CD 8（+）T细胞的早期肿瘤浸润和抗原特异性记忆T细胞的更大扩增。总之，激动性抗4-1BB mAb联合GM-CSF分泌性肿瘤细胞免疫治疗可能为癌症患者提供一种新的有效治疗策略。(c)2007年爱思唯尔公司All rights reserved.
Immunization with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific and long lasting anti-tumor immunity in clinical and preclinicat settings. Efforts to further increase immunotherapy efficacy with immune-modulatory agents are under evaluation. Based on the immune-modulatory properties of 4-1BB (CD137), it has been postulated that agonistic 4-1BB antibodies may add additional anti-tumor efficacy to GM-CSF-secreting tumor cell immunotherapy. The combination of GM-CSF-secreting tumor cell immunotherapy and anti-4-1BB monoclonal antibody (mAb) treatment resulted in rejection of established tumors in the B16 melanoma model. These anti-tumor effects correlated with persistent tumor-specific CD8(+) T cell responses. In addition, early tumor infiltration of functional CD8(+) T cells and a greater expansion of antigen-specific memory T cells were found in mice treated with the combination therapy. In summary, an agonistic anti-4-1BB mAb combined with GM-CSF-secreting tumor cell immunotherapy may provide a novel and potent treatment strategy for patients with cancer. (c) 2007 Elsevier Inc. All rights reserved.