CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems
CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems
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DOI：
10.1016/j.vaccine.2003.10.048
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发表时间：
2004-04-16
期刊：
影响因子：
5.5
通讯作者：
Houghton, AN
中科院分区：
文献类型：
--
作者：
Gregor, PD;Wolchok, JD;Houghton, AN
异种DNA疫苗可以通过T细胞和抗体依赖性效应机制诱导肿瘤免疫。CTLA-4与APC上表达的B7结合的阻断已显示增强T细胞依赖性免疫。我们研究了CTLA-4阻断是否可以增加DNA疫苗引起的T细胞应答和肿瘤免疫。CTLA-4阻断增强了针对黑色素瘤分化抗原酪氨酸酶相关蛋白2和gp 100免疫的小鼠中的B 16肿瘤排斥，并且当抗CTLA-4与加强疫苗接种一起施用时，这种效果更强。CTLA-4阻断也增加了T细胞对前列腺特异性膜抗原（PSMA）的反应，当给予第二次或第三次疫苗接种时。基于这些临床前研究，我们建议，抗CTLA-4应测试与异种DNA疫苗的癌症，并应特别注意的顺序和时间表的管理。(C)2004爱思唯尔有限公司保留所有权利。
Xenogeneic DNA vaccination can elicit tumor immunity through T cell and antibody-dependent effector mechanisms. Blockade of CTLA-4 engagement with B7 expressed on APCs has been shown to enhance T cell-dependent immunity. We investigated whether CTLA-4 blockade could increase T-cell responses and tumor immunity elicited by DNA vaccines. CTLA-4 blockade enhanced B 16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations. CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination. Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration. (C) 2004 Elsevier Ltd. All rights reserved.