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Biopolymer implants enhance the efficacy of adoptive T cell therapy

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 their inefficient expansion in the immunosuppressive tumor microenvironment. Here we describe a bioactive polymer...

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Autores principales: Stephan, Sirkka B., Taber, Alexandria M., Jileaeva, Ilona, Pegues, Ericka P., Sentman, Charles L., Stephan, Matthias T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289408/
https://www.ncbi.nlm.nih.gov/pubmed/25503382
http://dx.doi.org/10.1038/nbt.3104
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author Stephan, Sirkka B.
Taber, Alexandria M.
Jileaeva, Ilona
Pegues, Ericka P.
Sentman, Charles L.
Stephan, Matthias T.
author_facet Stephan, Sirkka B.
Taber, Alexandria M.
Jileaeva, Ilona
Pegues, Ericka P.
Sentman, Charles L.
Stephan, Matthias T.
author_sort Stephan, Sirkka B.
collection PubMed
description 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 their 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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spelling pubmed-42894082015-07-01 Biopolymer implants enhance the efficacy of adoptive T cell therapy Stephan, Sirkka B. Taber, Alexandria M. Jileaeva, Ilona Pegues, Ericka P. Sentman, Charles L. Stephan, Matthias T. Nat Biotechnol Article 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 their 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. 2014-12-15 2015-01 /pmc/articles/PMC4289408/ /pubmed/25503382 http://dx.doi.org/10.1038/nbt.3104 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Stephan, Sirkka B.
Taber, Alexandria M.
Jileaeva, Ilona
Pegues, Ericka P.
Sentman, Charles L.
Stephan, Matthias T.
Biopolymer implants enhance the efficacy of adoptive T cell therapy
title Biopolymer implants enhance the efficacy of adoptive T cell therapy
title_full Biopolymer implants enhance the efficacy of adoptive T cell therapy
title_fullStr Biopolymer implants enhance the efficacy of adoptive T cell therapy
title_full_unstemmed Biopolymer implants enhance the efficacy of adoptive T cell therapy
title_short Biopolymer implants enhance the efficacy of adoptive T cell therapy
title_sort biopolymer implants enhance the efficacy of adoptive t cell therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289408/
https://www.ncbi.nlm.nih.gov/pubmed/25503382
http://dx.doi.org/10.1038/nbt.3104
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