Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines.
Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines.
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发表时间：
1996-06
期刊：
影响因子：
11.2
通讯作者：
Ronald S. Chamberlain;M. Carroll;V. Bronte;P. Hwu;Steven Warren;J. C. Yang;M. Nishimura;B. Moss;S. Rosenberg;N. Restifo
中科院分区：
文献类型：
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作者：
Ronald S. Chamberlain;M. Carroll;V. Bronte;P. Hwu;Steven Warren;J. C. Yang;M. Nishimura;B. Moss;S. Rosenberg;N. Restifo
在缺乏共刺激信号的情况下 T 淋巴细胞的激活可能导致细胞无反应或凋亡。能够提供共刺激信号的两种分子 B7-1 (CD80) 和 B7-2 (CD86) 已被证明可以增强全肿瘤细胞疫苗的免疫原性。为了探索共刺激在重组抗癌疫苗设计中的潜在作用，我们使用 lacZ 转导的 CT26 作为实验肿瘤，并使用 β-半乳糖苷酶 (β-gal) 作为模型肿瘤抗原。通过与表达鼠 B7-1 的 rVV 混合来增强表达 β-gal 的重组痘苗病毒 (rVV) 的功能的尝试没有成功。然而，当给荷有肿瘤的小鼠施用3或6天时，设计表达B7-1和模型抗原β-gal的双重组牛痘病毒能够显着减少肺转移的数量。最重要的是，双重组牛痘病毒延长了荷瘤小鼠的存活时间。这些作用是抗原特异性的。相关的共刺激分子 B7-2 被发现对表达 β-gal 的 rVV 的功能具有类似的增强作用，尽管不太令人印象深刻。因此，向编码模型抗原的rVV添加B7-1和较小程度的B7-2显着增强了这些基于痘病毒的治疗性抗癌疫苗的治疗性抗肿瘤效果。
Activation of T lymphocytes in the absence of a costimulatory signal can result in anergy or apoptotic cell death. Two molecules capable of providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have been shown to augment the immunogenicity of whole-tumor cell vaccines. To explore a potential role for costimulation in the design of recombinant anticancer vaccines, we used lacZ-transduced CT26 as an experimental tumor and beta-galactosidase (beta-gal) as the model tumor antigen. Attempts to augment the function of a recombinant vaccinia virus (rVV) expressing beta-gal by admixture with rVV expressing murine B7-1 were unsuccessful. However, a double recombinant vaccinia virus engineered to express both B7-1 and the model antigen beta-gal was capable of significantly reducing the number of pulmonary metastases when administered to mice bearing tumors established for 3 or 6 days. Most important, the double recombinant vaccinia virus prolonged the survival of tumor-bearing mice. These effects were antigen specific. The related costimulatory molecule B7-2 was found to have a similar, although less impressive enhancing effect on the function of a rVV expressing beta-gal. Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV encoding a model antigen significantly enhanced the therapeutic antitumor effects of these poxvirus-based, therapeutic anticancer vaccines.