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Nat Nanotechnol ; 16(2): 214-223, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33318641

RESUMO

Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell-engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micrometre-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells. Locally retained ICEp presenting a high density of priming antigens activated CAR T cells, driving local tumour clearance while sparing uninjected tumours in immunodeficient mice. The ratiometric control of costimulatory ligands (anti-CD3 and anti-CD28 antibodies) and the surface presentation of a cytokine (IL-2) on ICEp were shown to substantially impact human primary T cell activation phenotypes. This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies.


Assuntos
Materiais Biocompatíveis/química , DNA/química , Linfócitos T/imunologia , Animais , Apresentação de Antígeno , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Humanos , Imunoterapia Adotiva , Ativação Linfocitária , Camundongos , Nanopartículas/química , Neoplasias/terapia , Proteínas/química , Proteínas/imunologia , Proteínas/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/transplante
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