Anti‐angiogenic therapy subsequent to adeno‐associated‐virus‐mediated immunotherapy eradicates lymphomas that disseminate to the liver
Anti‐angiogenic therapy subsequent to adeno‐associated‐virus‐mediated immunotherapy eradicates lymphomas that disseminate to the liver
复制标题
腺相关病毒介导的免疫治疗后的抗血管生成治疗可根除播散至肝脏的淋巴瘤
DOI：
10.1002/ijc.20624
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发表时间：
2005
影响因子：
6.4
通讯作者：
R. Xu
中科院分区：
文献类型：
--
作者：
Xueying Sun;G. Krissansen;P. Fung;Sue Xu;Juan Shi;K. Man;S. Fan;R. Xu
肝癌的预后非常差，缺乏有效的治疗。我们之前已经证明，门静脉内注射表达血管抑素的腺相关病毒（AAV）颗粒导致血管抑素的长期表达，能够抑制肝脏中EL-4肿瘤的生长。在这里，我们通过使用编码T细胞共刺激因子B7.1的AAV载体将联合收割机AAV介导的血管抑制素治疗与免疫治疗相结合。用AAV-B7. 1病毒孵育EL-4细胞导致B7.1在80%的EL-4细胞表面上快速表达。接种B7.1工程肿瘤细胞的小鼠排斥肿瘤细胞，并抵抗未经修饰的亲本细胞的二次攻击。来自接种小鼠的脾细胞在体外对亲代EL-4细胞具有高度细胞毒性。然而，接种疫苗的小鼠未能抵抗EL-4细胞的沉重负担的挑战。将表达血管抑素的AAV颗粒门静脉内注射到1个月前接种B7.1工程肿瘤细胞的小鼠中，保护小鼠免受EL-4细胞的重负荷的攻击，并根除了已扩散到肝脏的肿瘤。联合治疗提高了晚期肝癌小鼠的生存率。这些令人鼓舞的结果保证了在癌症免疫治疗后使用抗血管生成治疗靶向不可切除的播散性肝转移的研究。
Liver cancer has a very poor prognosis and lacks effective therapy. We have previously demonstrated that intraportal injection of adeno‐associated‐viral (AAV) particles that express angiostatin lead to long‐term expression of angiostatin capable of suppressing the outgrowth of EL‐4 tumors in the liver. Here we combine AAV‐mediated angiostatin therapy with immunotherapy by employing an AAV vector encoding the T‐cell costimulator B7.1. Incubation of EL‐4 cells with AAV‐B7.1 viruses resulted in the rapid expression of B7.1 on the surface of 80% of EL‐4 cells. Mice that were vaccinated with B7.1‐engineered tumor cells rejected the tumor cells and resisted a secondary challenge with unmodified parental cells. Splenocytes from the vaccinated mice were highly cytotoxic towards parental EL‐4 cells in vitro. However, the vaccinated mice failed to resist the challenge of a heavy burden of EL‐4 cells. Intraportal injection of AAV particles that express angiostatin into mice that had been vaccinated 1 month earlier with B7.1‐engineered tumor cells protected mice against the challenge of a heavy burden of EL‐4 cells and eradicated tumors that had disseminated to the liver. The combinational therapy increased the survival rate of mice with advanced liver cancer. These encouraging results warrant investigation of the employment of anti‐angiogenic therapy subsequent to cancer immunotherapy for targeting unresectable disseminated liver metastases.
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影响因子：
12.4
作者：
Pawliuk, R;Bachelot, T;Leboulch, P
通讯作者：
Leboulch, P
影响因子：
12.4
作者：
Eisterer, W;Jiang, XY;Eaves, C
通讯作者：
Eaves, C
影响因子：
56.9
作者：
TOWNSEND, SE;ALLISON, JP
通讯作者：
ALLISON, JP
膀胱内基因治疗：使用重组牛痘病毒载体进行体内基因转移。
影响因子：
11.2
作者：
Lee,SS;Eisenlohr,LC;McCue,PA;Mastrangelo,MJ;Lattime,EC
通讯作者：
Lattime,EC
给药途径决定了对腺相关病毒载体的 T 细胞依赖性体液反应的诱导。
DOI：
10.1006/mthe.2000.0045
发表时间：
2000
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy.
影响因子：
--
作者：
Xiao,W;Chirmule,N;Schnell,MA;Tazelaar,J;Hughes,JV;Wilson,JM
通讯作者：
Wilson,JM