A single intratumoral injection of a fiber-mutant adenoviral vector encoding interleukin 12 induces remarkable anti-tumor and anti-metastatic activity in mice with Meth-A fibrosarcoma.
A single intratumoral injection of a fiber-mutant adenoviral vector encoding interleukin 12 induces remarkable anti-tumor and anti-metastatic activity in mice with Meth-A fibrosarcoma.
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DOI：
10.1016/j.bbrc.2005.01.061
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发表时间：
2005-03
影响因子：
3.1
通讯作者：
Jianqing Gao;T. Sugita;N. Kanagawa;Keisuke Iida;Y. Eto;Yoshiaki Motomura;H. Mizuguchi;Y. Tsutsumi;T. Hayakawa;T. Mayumi;S. Nakagawa
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文献类型：
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作者：
Jianqing Gao;T. Sugita;N. Kanagawa;Keisuke Iida;Y. Eto;Yoshiaki Motomura;H. Mizuguchi;Y. Tsutsumi;T. Hayakawa;T. Mayumi;S. Nakagawa
细胞因子编码的病毒载体在肿瘤基因免疫治疗中具有广阔的应用前景。白介素12(IL-12)已被广泛应用于抗肿瘤治疗，但给药途径和肿瘤特性对治疗效果有很大影响。Meth-A纤维肉瘤已被证明通过全身给药对IL-12治疗不敏感。在本研究中，我们构建了一种编码IL-12的纤维突变型腺病毒载体(AdRGD-IL-12)，该载体在Meth-A肿瘤细胞中显示了较高的基因转染率，并用ELISA法证实了其培养上清液中IL-12p70的产生。在治疗实验中，一次低剂量(2×107个空斑形成单位)的AdRGD-IL-12瘤内注射可产生显著的抗肿瘤活性，并显著延长Meth-A纤维肉瘤小鼠的生存时间。免疫组织化学染色显示，IL-12载体可诱导T细胞在肿瘤组织中聚集。此外，瘤内注射该载体可诱导抗转移效应和对同种肿瘤攻击的长期特异性免疫。
Cytokine-encoding viral vectors are considered to be promising in cancer gene immunotherapy. Interleukin 12 (IL-12) has been used widely for anti-tumor treatment, but the administration route and tumor characteristics strongly influence therapeutic efficiency. Meth-A fibrosarcoma has been demonstrated to be insensitive to IL-12 treatment via systemic administration. In the present study, we developed an IL-12-encoding fiber-mutant adenoviral vector (AdRGD-IL-12) that showed enhanced gene transfection efficiency in Meth-A tumor cells, and the production of IL-12 p70 in the culture supernatant from transfected cells was confirmed by ELISA. In therapeutic experiments, a single low-dose (2×107plaque-forming units) intratumoral injection of AdRGD-IL-12 elicited pronounced anti-tumor activity and notably prolonged the survival of Meth-A fibrosarcoma-bearing mice. Immunohistochemical staining revealed that the IL-12 vector induced the accumulation of T cells in tumor tissue. Furthermore, intratumoral administration of the vector induced an anti-metastasis effect as well as long-term specific immunity against syngeneic tumor challenge.