Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer
Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer
复制标题
低剂量紫杉醇增强 GM-CSF 表面修饰的全肿瘤细胞疫苗对前列腺癌小鼠模型的抗肿瘤功效
DOI：
10.1007/s00262-011-0988-4
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发表时间：
2011-05-01
影响因子：
5.8
通讯作者：
Gao, Jimin
中科院分区：
文献类型：
--
作者：
He, Qiushan;Li, Jinlong;Gao, Jimin
化疗联合肿瘤疫苗是一种很有吸引力的癌症治疗方法。本研究旨在探讨新型GM-CSF(粒细胞-巨噬细胞集落刺激因子)表面修饰的肿瘤细胞疫苗联合紫杉醇治疗小鼠RM-1前列腺癌的最佳方案和作用机制。首先，检测了不同剂量紫杉醇(4、20、40 mg/kg)与不同给药顺序的疫苗在小鼠RM-1前列腺癌模型中的抗肿瘤效果。观察不同剂量紫杉醇在体内和体外对RM-1细胞、T细胞和树突状细胞的影响。结果表明：(A)GM-CSF表面修饰的肿瘤细胞疫苗诱导DC摄取肿瘤抗原的能力强于照射后的肿瘤细胞和游离的GM-CSF，紫杉醇4 mg/kg联合GM-CSF表面修饰的肿瘤细胞疫苗在紫杉醇后2天给药对RM-1前列腺癌小鼠的肿瘤消退最有效；(C)接种紫杉醇4 mg/kg后，肿瘤组织中CD8(+)T细胞的浸润率最高，提示诱导了肿瘤特异性免疫反应。这些发现表明，GM-CSF表面修饰的肿瘤细胞疫苗与紫杉醇联合应用可能对前列腺癌患者具有潜在的临床益处。此外，免疫化疗的效果取决于紫杉醇剂量和紫杉醇/疫苗给药顺序的仔细选择。
Chemotherapy combined with a tumor vaccine is an attractive approach in cancer therapy. This study was designed to investigate the optimal schedule and mechanisms of action of a novel GM-CSF (granulocyte-macrophage colony-stimulating factor) surface-modified tumor-cell vaccine in combination with paclitaxel in the treatment of mouse RM-1 prostate cancer. First, the anti-tumor efficiencies of various dosage of paclitaxel (4, 20, 40 mg/kg) in combination with the vaccine in different administration sequences were examined in the mouse RM-1 prostate cancer model. Then, the in vivo and in vitro effects of various dosage of paclitaxel on RM-1 cells, T cells, and DCs (dendritic cells) were evaluated. The results showed that: (a) the GM-CSF-surface-modified tumor-cell vaccine was more potent at inducing the uptake of tumor antigens by DCs than irradiated tumor cells plus free GM-CSF; (b) 4 mg/kg paclitaxel combined with the GM-CSF-surface-modified tumor-cell vaccine was the most effective at enhancing tumor regression in RM-1 prostate cancer mice when the vaccine was administrated 2 days after paclitaxel; and (c) administration of 4 mg/kg paclitaxel followed by the vaccine induced the highest degree of CD8(+) T-cell infiltration in tumor tissue, suggesting that the induction of tumor-specific immune response had occurred. These findings suggested that the GM-CSF-surface-modified tumor-cell vaccine may have potential clinical benefit for patients with prostate cancer when it is combined with paclitaxel. Furthermore, the effect of immunochemotherapy depends on careful selection of paclitaxel dosage and the sequence of paclitaxel/vaccine administration.