Ma Qing, Zhou Dapeng, DeLyria Elizabeth S, Wen Xiaoxia, Lu Wei, Thapa Prakash, Liu Chengwen, Li Dan, Bassett Roland L, Overwijk Willem W, Hwu Patrick, Li Chun
Departments of *Stem Cell Transplantation and Cellular Therapy †Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China ‡Melanoma Medical Oncology §Cancer Systems Imaging ∥Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
J Immunother. 2017 Jan;40(1):11-20. doi: 10.1097/CJI.0000000000000145.
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.
迫切需要新的临床适用药物递送方法,以增强免疫激活药物在肿瘤中的蓄积。我们合成了聚(L-谷氨酸)-CpG ODN2216缀合物(PG-CpG),并将其瘤内注射到携带皮下B16-卵清蛋白黑色素瘤的C57BL/6小鼠体内。在这个成熟的实体瘤模型中,就减少肿瘤生长和触发抗原特异性CD8 T细胞反应而言,PG-CpG引发了与CpG相同的强效抗肿瘤活性。此外,瘤内注射后,PG-CpG在肿瘤和引流淋巴结中的保留时间明显长于游离CpG。具体而言,注射后48小时,注射剂量的26.5%±16.9%的PG-CpG留在肿瘤中,而游离CpG为4.72%±2.61%;1.53%±1.22%的注射PG-CpG保留在引流的腹股沟淋巴结中,而游离CpG为0.37%±0.33%。这些发现表明,PG是一种有效的合成聚合物载体,可用于将免疫刺激剂递送至肿瘤和淋巴结。
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