Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma.
Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma.
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合成聚（L-谷氨酸）缀合的 CpG 具有抗肿瘤功效，在黑色素瘤小鼠模型中进行瘤内注射后，肿瘤中的滞留和引流淋巴结增加
DOI：
10.1097/cji.0000000000000145
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Li C
中科院分区：
文献类型：
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作者：
Ma Q;Zhou D;DeLyria ES;Wen X;Lu W;Thapa P;Liu C;Li D;Bassett RL;Overwijk WW;Hwu P;Li C
迫切需要新的临床适用的药物递送方法来增强免疫激活药物在肿瘤中的积累。我们合成了一种聚（L-谷氨酸）-CpG ODN 2216偶联物（PG-CpG），并将其瘤内注射到皮下B16-卵白蛋白黑色素瘤的C57 BL/6小鼠中。PG-CpG在该良好建立的实体瘤模型中在减少肿瘤生长和触发抗原特异性CD 8 + T细胞应答方面引起与CpG相同的有效抗肿瘤活性。此外，PG-CpG在肿瘤内注射后在肿瘤和引流淋巴结中的保留时间显著长于游离CpG。具体地，注射后48小时，注射的PG-CpG剂量的26.5%±16.9%相对于游离CpG的4.72%±2.61%保留在肿瘤处，并且注射的PG-CpG的1.53%±1.22%相对于游离CpG的0.37%±0.33%保留在引流腹股沟淋巴结中。这些发现表明PG是一种有效的合成聚合物载体，用于将免疫刺激剂递送至肿瘤和淋巴结。
There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8+ T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 hours after injection, 26.5%±16.9% of the injected PG-CpG dose versus 4.72%±2.61% of free CpG remained at the tumor, and 1.53%±1.22% of the injected PG-CpG versus 0.37%±0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes.