The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling
The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling
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DOI：
10.1016/j.canlet.2005.02.005
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发表时间：
2006-01-18
期刊：
影响因子：
9.7
通讯作者：
Claesson, MH
中科院分区：
文献类型：
--
作者：
Met, Ö;Wang, MJ;Claesson, MH
树突状细胞（DC）用H-2K（h）结合OVA（257-264）-肽（SIINFEKL）脉冲，并使用其一次注射疫苗与抗CTLA-4单克隆抗体（mAb）组合来治疗3天前接种3 × 105个E.G7-OVA淋巴瘤细胞的小鼠。单独的DC疫苗接种或CTLA-4阻断都不能防止肿瘤攻击小鼠中的肿瘤生长。相比之下，一次疫苗接种和注射抗CTLA-4 mAb的组合导致超过60%的小鼠的排斥或肿瘤生长延迟。OVA转基因或SIINFEKL表位在接种疫苗的小鼠的进展性肿瘤中没有丢失，然而，在IFN-γ ELISPOT测定中，仅在显示完全肿瘤排斥的小鼠中发现宿主CTL的最高程度的抗SIINFEKL反应性。具有排斥E.G7-OVA肿瘤的疫苗接种小鼠能够排斥随后用1 × 10（6）E.G7-OVA肿瘤细胞的攻击，并且随后这些小鼠甚至排斥野生型EL-4肿瘤细胞，表明在疫苗接种诱导的E.G7-OVA排斥过程中发生肿瘤表位扩散。与这些观察结果一致，排斥E.G7-OVA肿瘤的小鼠在脾和骨髓中显示出对FIINFEKL-肽和其他EL-4衍生的肿瘤排斥表位的持久CTL记忆。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Dendritic eel Is (DCs) Were pulsed with the H-2K(h) binding OVA(257-264)-peptide (SIINFEKL), and used its one single-injection vaccine in combination with anti-CTLA-4 monoclonal antibody (mAb) to treat mice inoculated 3 days previously with 3 x 10(5) E.G7-OVA lymphoma cells. Neither DC vaccination nor CTLA-4 blockage alone prevented tumor growth in tumor challenged mice. In contrast, the combination of one vaccination and injection of anti-CTLA-4 mAb lead to rejection or retarded tumor growth in more than 60% of the mice. The OVA-transgene or the SIINFEKL-epitope was not lost in the progressing tumors of vaccinated mice, however, the highest degree of anti-SIINFEKL reactivity of host CTLs in an IFN-gamma ELISPOT assay was found only in mice showing complete tumor rejection. Vaccinated mice having rejected E.G7-OVA tumors were capable of rejecting subsequent challenges with 1 x 10(6) E.G7-OVA tumor cells, and later on these mice even rejected wild-type EL-4 tumor cells indicating that tumor epitope spreading takes Place during the process of vaccination-induced E.G7-OVA rejection. In agreement with these observations, mice having rejected E.G7-OVA tumors showed long lasting CTL memory in spleen and bone marrow towards both file SIINFEKL-peptide and other EL-4-derived tumor rejecting epitopes. (c) 2005 Elsevier Ireland Ltd. All rights reserved.