An Ad5[E1-, E2b-]-HER2/neu vector induces immune responses and inhibits HER2/neu expressing tumor progression in Ad5 immune mice.
An Ad5[E1-, E2b-]-HER2/neu vector induces immune responses and inhibits HER2/neu expressing tumor progression in Ad5 immune mice.
复制标题
DOI：
10.1038/cgt.2010.82
复制
发表时间：
2011-05
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫疗法是治疗癌症的一种很有前途的方法。修饰腺病毒5 （Ad5）载体已被用作传递编码TAA基因的平台。Ad5载体免疫治疗的一个主要障碍是在给药后或存在预先存在的Ad5免疫诱导媒介免疫，从而导致媒介减轻。我们已经报道了在E1， E2b和E3区域具有独特缺失的Ad5 [E1-， E2b-]平台可以在存在预先存在的Ad5免疫的情况下诱导对递送的转基因产品的有效细胞介导免疫（CMI）。在这里，我们报告使用表达TAA HER2/neu的Ad5 [E1-， E2b-]载体平台作为乳腺癌免疫治疗剂。Ad5 [E1-， E2b-]-HER2/neu诱导Ad5 naïve和Ad5免疫小鼠抗HER2/neu强效CMI。体外实验还诱导了体液反应，抗体可以在补体存在的情况下裂解表达HER2/neu的肿瘤细胞。在Ad5 naïve和Ad5免疫小鼠模型中，Ad5 [E1-， E2b-]-HER2/neu阻止表达HER2/neu的肿瘤的建立，并显著抑制已建立肿瘤的进展。这些数据表明，体内递送Ad5 [E1-， E2b-]-HER2/neu可以诱导抗taa免疫并抑制表达HER2/neu的癌症的进展。
Immunotherapy is a promising approach for the treatment of cancers. Modified Adenovirus 5 (Ad5) vectors have been used as a platform to deliver genes encoding TAA. A major obstacle to Ad5 vector immunotherapy has been the induction of vector immunity following administration or the presence of pre-existing Ad5 immunity, which results in vector mitigation. It has been reported by us that the Ad5 [E1-, E2b-] platform with unique deletions in the E1, E2b and E3 regions can induce potent cell mediated immunity (CMI) against delivered transgene products in the presence of pre-existing Ad5 immunity. Here we report the use of an Ad5 [E1-, E2b-] vector platform expressing the TAA HER2/neu as a breast cancer immunotherapeutic agent. Ad5 [E1-, E2b-]-HER2/neu induced potent CMI against HER2/neu in Ad5 naïve and Ad5 immune mice. Humoral responses were also induced and antibodies could lyse HER2/neu expressing tumor cells in the presence of complement in vitro. Ad5 [E1-, E2b-]-HER2/neu prevented establishment of HER2/neu-expressing tumors and significantly inhibited progression of established tumors in Ad5 naïve and Ad5 immune murine models. These data demonstrate that in vivo delivery of Ad5 [E1-, E2b-]-HER2/neu can induce anti-TAA immunity and inhibit progression of HER2/neu expressing cancers.