Format

Send to

Choose Destination
Nat Biotechnol. 2015 Jan;33(1):97-101. doi: 10.1038/nbt.3104. Epub 2014 Dec 15.

Biopolymer implants enhance the efficacy of adoptive T-cell therapy.

Author information

1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
2
Technology Access Foundation (TAF) Academy, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
3
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
4
1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Technology Access Foundation (TAF) Academy, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [3] Department of Bioengineering and Molecular Engineering &Sciences Institute, University of Washington, Seattle, Washington, USA. [4] Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington, USA.

Abstract

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.

PMID:
25503382
PMCID:
PMC4289408
DOI:
10.1038/nbt.3104
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center