Combination immunotherapy with 4-1BBL and CTLA-4 blockade for the treatment of prostate cancer.

Combination immunotherapy with 4-1BBL and CTLA-4 blockade for the treatment of prostate cancer.
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DOI:
10.1155/2012/439235
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发表时间:
2012
影响因子:
--
通讯作者:
Hengchen Z
Hengchen Z
中科院分区:
其他
文献类型:
--
作者:
Youlin K;Li Z;Xiaodong W;Xiuheng L;Hengchen Z

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免疫调节已被证明与一些小鼠肿瘤的进行性生长有关。通过激活4-1BB或阻断细胞毒性T淋巴细胞相关抗原-4(CTLA-4)来阻断免疫调节通路似乎是一种很有前途的癌症免疫治疗策略。在本研究中,我们检测了表达4-1BBL的肿瘤细胞疫苗联合CTLA-4阻断对小鼠前列腺癌RM-1的排斥反应的效果。我们发现,与单独使用任何一种治疗方法相比,由4-1BBL表达的RM-1细胞组成的疫苗和CTLA-4阻断联合使用可以导致RM-1肿瘤的消退,并显著提高肿瘤细胞接受者的存活率。联合免疫可提高对RM-1细胞的杀伤活性,增加混合培养上清液中干扰素-γ、肿瘤坏死因子-α和IL-2的分泌。这些结果提示,联合激活4-1BB和阻断CTLA-4可能为前列腺癌的免疫治疗提供一种新的策略。
Immune regulation has been shown to be involved in the progressive growth of some murine tumours. Interruption of immune regulatory pathways via activation of 4-1BB or cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade appears to be a promising strategy for cancer immunotherapy. In this study, we examined the effectiveness of 4-1BBL-expressing tumor cell vaccine in combination with CTLA-4 blockade on rejection of murine prostate cancer RM-1. We found that the combination of both a vaccine consisting of 4-1BBL-expressing RM-1 cells and CTLA-4 blockade resulted in regression of RM-1 tumors and a significant increase in survival of the tumour cell recipients, compared to that of either treatment alone. The combined vaccination resulted in higher CTL against RM-1 cells and increased secretion of IFN-γ, TNF-α, and IL-2 in the mix-cultured supernatant. These results suggest that combining activation of 4-1BB and blockade of CTLA-4 may offer a new strategy for prostate cancer immunotherapy.
CTLA-4 阻断和 4-1BB 激活相结合,通过增加 T 细胞浸润、增殖和细胞因子产生来增强肿瘤排斥。
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