title: Biopolymer implants enhance the efficacy of adoptive T-cell therapy.
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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Sirkka B
authors.initials: SB
authors.lastname: Stephan
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Alexandria M
authors.initials: AM
authors.lastname: Taber
authors.affiliation: Technology Access Foundation (TAF) Academy, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Jileaeva
authors.affiliation: Technology Access Foundation (TAF) Academy, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Ericka P
authors.initials: EP
authors.lastname: Pegues
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sentman
authors.affiliation: 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.
authors.forename: Matthias T
authors.initials: MT
authors.lastname: Stephan
mesh_terms: D019264:Adoptive Transfer; D001704:Biopolymers; D019736:Prostheses and Implants; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001704:Biopolymers