CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity.
CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity.
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DOI：
10.1007/s00262-011-0973-y
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Klinman DM
中科院分区：
文献类型：
--
作者：
Shirota H;Klinman DM
癌症免疫治疗的主要目标是诱导一种能够根除已建立的肿瘤并防止肿瘤转移的免疫反应。实现这一目标的一种策略是利用全部被杀死的肿瘤细胞作为主要免疫原。被杀死的肿瘤细胞提供了肿瘤相关抗原(TAA)的全面来源，从而消除了识别单个抗原的需要。不幸的是，被杀死的肿瘤细胞的免疫原性往往很差。为了克服这一局限性，我们将免疫刺激CpG寡核苷酸(ODN)与凋亡的肿瘤细胞共价偶联，并检测了它们诱导TAA特异性免疫反应的能力。结果表明，CpG结合增强了树突状细胞(DC)对细胞疫苗的摄取，上调了共刺激分子的表达，并促进了免疫刺激细胞因子的产生。接种CpG结合的肿瘤细胞可触发肿瘤特异性细胞毒性T淋巴细胞(CTL)的扩张，从而减少已建立的肿瘤的生长并防止其转移扩散。因此，将CpG ODN连接到基于细胞的肿瘤疫苗是提高癌症免疫治疗的重要一步。
The primary goal of cancer immunotherapy is to elicit an immune response capable of eradicating established tumors and preventing tumor metastasis. One strategy to achieve this goal utilizes whole killed tumor cells as the primary immunogen. Killed tumor cells provide a comprehensive source of tumor-associated antigens (TAAs), thereby eliminating the need to identify individual antigens. Unfortunately, killed tumor cells tend to be poorly immunogenic. To overcome this limitation, we covalently conjugated immunostimulatory CpG oligodeoxynucleotides (ODN) to apoptotic tumor cells and examined their ability to induce TAA-specific immune responses. Results indicate that CpG conjugation enhances the uptake of cell-based vaccines by dendritic cells (DCs), up-regulates co-stimulatory molecule expression, and promotes the production of immunostimulatory cytokines. Vaccination with CpG-conjugated tumor cells triggers the expansion of tumor-specific cytotoxic T lymphocytes (CTL) that reduce the growth of established tumors and prevents their metastatic spread. Thus, conjugating CpG ODN to cell-based tumor vaccines is an important step toward improving cancer immunotherapy.
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