Biopolymer implants enhance the efficacy of adoptive T-cell therapy

被引:401
作者
Stephan, Sirkka B. [1 ]
Taber, Alexandria M. [1 ]
Jileaeva, Ilona [2 ]
Pegues, Ericka P. [2 ]
Sentman, Charles L. [3 ]
Stephan, Matthias T. [1 ,2 ,4 ,5 ,6 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA
[2] Fred Hutchinson Canc Res Ctr, Technol Access Fdn TAF Acad, Seattle, WA 98104 USA
[3] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Lebanon, NH USA
[4] Univ Washington, Dept Bioengn & Mol Engn, Seattle, WA 98195 USA
[5] Univ Washington, Inst Sci, Seattle, WA 98195 USA
[6] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA 98195 USA
关键词
PHASE-I; IMMUNOTHERAPY; VIVO; SUPERAGONIST; RECEPTOR; PATIENT; IL-15;
D O I
10.1038/nbt.3104
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Although adoptive T-cell therapy holds promise for the treatment of many cancers, its clinical utility has been limited by problems in delivering targeted lymphocytes to tumor sites, and the cells' inefficient expansion in the immunosuppressive tumor microenvironment. Here we describe a bioactive polymer implant capable of delivering, expanding and dispersing tumor-reactive T cells. The approach can be used to treat inoperable or incompletely removed tumors by situating implants near them or at resection sites. Using a mouse breast cancer resection model, we show that the implants effectively support tumor-targeting T cells throughout resection beds and associated lymph nodes, and reduce tumor relapse compared to conventional delivery modalities. In a multifocal ovarian cancer model, we demonstrate that polymer-delivered T cells trigger regression, whereas injected tumor-reactive lymphocytes have little curative effect. Scaffold-based T-cell delivery may provide a viable treatment option for inoperable tumors and reduce the rate of metastatic relapse after surgery. npg (C) 2015 Nature America, Inc. All rights reserved.
引用
收藏
页码:97 / U277
页数:7
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