Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors

2017/04/23 by Tyrel T. Smith, Howell Moffett, Howell F. Moffett +10 · 336 citations
Engineering · Immunology and Microbiology · Medicine · #Biology #CAR-T cell therapy research #Cancer #Cancer cell #Cancer immunotherapy #Cancer research #Chimeric antigen receptor #Immune Cell Function and Interaction #Immune system #Immunology #Immunotherapy #Internal medicine #Medicine #Melanoma #Nanowire Synthesis and Applications #T cell #Tumor microenvironment

paper · pdf · doi:10.1172/jci87624

published in Journal of Clinical Investigation 127(6), 2176-2191 (American Society for Clinical Investigation)

openalex publication_date 2017/04/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04

Abstract

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.

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