title: Magnetic field-induced T cell receptor clustering by nanoparticles enhances T cell activation and stimulates antitumor activity.
abstract: Iron-dextran nanoparticles functionalized with T cell activating proteins have been used to study T cell receptor (TCR) signaling. However, nanoparticle triggering of membrane receptors is poorly understood and may be sensitive to physiologically regulated changes in TCR clustering that occur after T cell activation. Nano-aAPC bound 2-fold more TCR on activated T cells, which have clustered TCR, than on naive T cells, resulting in a lower threshold for activation. To enhance T cell activation, a magnetic field was used to drive aggregation of paramagnetic nano-aAPC, resulting in a doubling of TCR cluster size and increased T cell expansion in vitro and after adoptive transfer in vivo. T cells activated by nano-aAPC in a magnetic field inhibited growth of B16 melanoma, showing that this novel approach, using magnetic field-enhanced nano-aAPC stimulation, can generate large numbers of activated antigen-specific T cells and has clinically relevant applications for adoptive immunotherapy.
authors.affiliation: Department of Biomedical Engineering, ‡Institute of Cell Engineering, §Department of Biology, ⊥Department of Pathology, and ∥Departments of Oncology and Medicine, Johns Hopkins School of Medicine , Baltimore, Maryland, United States.
authors.forename: Karlo
authors.initials: K
authors.lastname: Perica
authors.forename: Ang
authors.initials: A
authors.lastname: Tu
authors.forename: Anne
authors.initials: A
authors.lastname: Richter
authors.forename: Joan Glick
authors.initials: JG
authors.lastname: Bieler
authors.forename: Michael
authors.initials: M
authors.lastname: Edidin
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schneck
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry; D016219:Immunotherapy, Adoptive; D007501:Iron / Q000737:chemistry / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D060526:Magnetic Fields; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D053758:Nanoparticles; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D003911:Dextrans; D011948:Receptors, Antigen, T-Cell; D007501:Iron