Therapeutic cell engineering with surface-conjugated synthetic nanoparticles

被引：655

作者：

Stephan, Matthias T. ^{[1
,2
]}

Moon, James J. ^{[1
,2
]}

Um, Soong Ho ^{[1
,2
,3
]}

Bershteyn, Anna ^{[1
,2
]}

Irvine, Darrell J. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA

[2] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[3] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[4] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA

[5] Harvard Univ, Boston, MA 02115 USA

[6] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

NATURE MEDICINE | 2010年 / 16卷 / 09期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

T-LYMPHOCYTES; STEM-CELLS; TRANSPLANTATION; ANTIGEN; IMPACT; CANCER; EXPANSION; TARGET; IL-15; TRIAL;

D O I：

10.1038/nm.2198

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A major limitation of cell therapies is the rapid decline in viability and function of the transplanted cells. Here we describe a strategy to enhance cell therapy via the conjugation of adjuvant drug-loaded nanoparticles to the surfaces of therapeutic cells. With this method of providing sustained pseudoautocrine stimulation to donor cells, we elicited marked enhancements in tumor elimination in a model of adoptive T cell therapy for cancer. We also increased the in vivo repopulation rate of hematopoietic stem cell grafts with very low doses of adjuvant drugs that were ineffective when given systemically. This approach is a simple and generalizable strategy to augment cytoreagents while minimizing the systemic side effects of adjuvant drugs. In addition, these results suggest therapeutic cells are promising vectors for actively targeted drug delivery.

引用

页码：1035 / U135

页数：8

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