期刊
BIOMATERIALS
卷 30, 期 35, 页码 6757-6767出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.08.037
关键词
Local tumor immunotherapy; IL-15 superagonist; Dendritic cells; Alginate; Hydrogels; Cancer vaccine
资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [U54-CA112967, U54-CA126515, U54 CA126515, U54 CA112967] Funding Source: Medline
- NIBIB NIH HHS [R01 EB007280-02, R01 EB007280-03, R01 EB007280, EB007280] Funding Source: Medline
Local immunotherapies are under investigation for the treatment of unresectable tumors and sites of solid tumor resection to prevent local recurrence. Successful local therapy could also theoretically elicit systemic immune responses against cancer. Here we explored the delivery of therapeutic dendritic cells (DCs), cytokines, or other immunostimulatory factors to tumors via the use of 'self-gelling' hydrogels based on the polysaccharide alginate, injected peritumorally around established melanoma lesions. Peritumoral injection of alginate matrices loaded with DCs and/or an interleukin-15 superagonist (IL-15SA) around 14-day established ova-expressing B16F0 murine melanoma tumors promoted immune cell accumulation in the peritumoral matrix, and matrix infiltration correlated with tumor infiltration by leukocytes. Single injections of IL-15SA-carrying gels concentrated the cytokine in the tumor site similar to 40-fold compared to systemic injection and enabled a majority of treated animals to suppress tumor growth for a week or more. Further, we found that single injections of alginate matrices loaded with IL-15SA and the Toll-like receptor ligand CpG or two injections of gels carrying IL-15SA alone could elicit comparable anti-tumor activity without the need for exogenous DCs. Thus, injectable alginate gels offer an attractive platform for local tumor immunotherapy, and facilitate combinatorial treatments designed to promote immune responses locally at a tumor site while limiting systemic exposure to potent immunomodulatory factors. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据