一种细胞因子递送聚合物在头颈部鳞状细胞癌小鼠模型中能有效减轻肿瘤负荷。
A cytokine-delivering polymer is effective in reducing tumor burden in a head and neck squamous cell carcinoma murine model.
作者信息
Lin Yuan, Luo Jie, Zhu Weichao Eric, Srivastava Minu, Schaue Dorthe, Elashoff David A, Dubinett Steven M, Sharma Sherven, Wu Benjamin, St John Maie A
机构信息
Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles, California, USA UCLA Head and Neck Cancer Program, University of California, Los Angeles, Los Angeles, California, USA Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA.
出版信息
Otolaryngol Head Neck Surg. 2014 Sep;151(3):447-53. doi: 10.1177/0194599814533775. Epub 2014 May 13.
OBJECTIVE
This study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC).
STUDY DESIGN
In vivo study.
SETTING
Academic research laboratory.
SUBJECTS AND METHODS
Mice were randomized to receive implantation of (1) no polymer, (2) plain polymer, (3) plain polymer with local cisplatin injection, or (4) cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days or (2) no radiation. For cytokine studies, mice were grouped into (1) no polymer, (2) plain polymer, (3) plain polymer with intratumoral injection of recombinant CCL21 twice a week, (4) polymer containing parental dendritic cells, or (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21).
RESULTS
The cisplatin-secreting polymer effectively reduced tumors in the mice by more than 16-fold (P < .01). We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to control groups. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by more than 41% (P < .01).
CONCLUSION
Herein, we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21 for a minimum of 5 days. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan to pursue prospective trials in patients with HNSCC.
目的
本研究旨在评估一种新型聚合物平台递送顺铂和细胞因子治疗头颈部鳞状细胞癌（HNSCC）的疗效。
研究设计
体内研究。
研究地点
学术研究实验室。
研究对象与方法
将小鼠随机分为四组，分别接受以下植入物：（1）无聚合物；（2）普通聚合物；（3）局部注射顺铂的普通聚合物；（4）顺铂聚合物。将植入顺铂聚合物或无聚合物的两组小鼠进一步随机分为两组，分别接受：（1）4天内每天4格雷的外照射；（2）不进行照射。对于细胞因子研究，将小鼠分为五组：（1）无聚合物；（2）普通聚合物；（3）每周两次瘤内注射重组CCL21的普通聚合物；（4）含亲本树突状细胞的聚合物；（5）含分泌CCL21的树突状细胞（DC-CCL21）的聚合物。
结果
分泌顺铂的聚合物使小鼠肿瘤有效缩小超过16倍（P <.01）。我们还观察到，与对照组相比，接受顺铂聚合物并同时接受放疗的小鼠肿瘤重量在统计学上显著更低。DC-CCL21聚合物使C3H/HeJ小鼠的SCCVII/SF肿瘤缩小超过41%（P <.01）。
结论
在此，我们证明了一种新型聚合物平台递送顺铂和细胞因子的疗效。我们还证明，我们能够在聚合物中有效地培养树突状细胞，使其至少5天内持续主动分泌CCL21。这种聚合物可能代表了一种针对HNSCC患者的新治疗方式。一旦这种聚合物平台得到优化，我们计划对头颈部鳞状细胞癌患者开展前瞻性试验。
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