Biopolymer implants enhance the efficacy of adoptive T-cell therapy

SB Stephan, AM Taber, I Jileaeva, EP Pegues… - Nature …, 2015 - nature.com
SB Stephan, AM Taber, I Jileaeva, EP Pegues, CL Sentman, MT Stephan
Nature biotechnology, 2015nature.com
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 …
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.
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