title: Nanoscale artificial antigen presenting cells for T cell immunotherapy.
abstract: Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for both adoptive and active immunotherapy. Thus far, aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to micron-sized beads. Nanoscale platforms have different trafficking and biophysical interaction properties and may allow development of new immunotherapeutic strategies. We therefore manufactured aAPC based on two types of nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles (50-100 nm in diameter) and avidin-coated quantum dot nanocrystals (~30 nm). Nanoscale aAPC induced antigen-specific T cell proliferation from mouse splenocytes and human peripheral blood T cells. When injected in vivo, both iron-dextran particles and quantum dot nanocrystals enhanced tumor rejection in a subcutaneous mouse melanoma model. This is the first description of nanoscale aAPC that induce antigen-specific T cell proliferation in vitro and lead to effective T cell stimulation and inhibition of tumor growth in vivo.
  
  
  BACKGROUND
  Artifical antigen presenting cells could revolutionize the field of cancer-directed immunotherapy. This team of investigators have manufactured two types of nanoscale particle platform-based aAPCs and demonstrates that both iron-dextran particles and quantum dot nanocrystals enhance tumor rejection in a melanoma model, providing the first description of nanoscale aAPCs that lead to effective T cell stimulation and inhibition of tumor growth.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Karlo
authors.initials: K
authors.lastname: Perica
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Andrés
authors.initials: A
authors.lastname: De León Medero
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Malarvizhi
authors.initials: M
authors.lastname: Durai
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Yen Ling
authors.initials: YL
authors.lastname: Chiu
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Joan Glick
authors.initials: JG
authors.lastname: Bieler
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Sibener
authors.affiliation: Miltenyi Biotec, Bergisch Gladbach, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Niemöller
authors.affiliation: Miltenyi Biotec, Bergisch Gladbach, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Assenmacher
authors.affiliation: Miltenyi Biotec, Bergisch Gladbach, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Richter
authors.affiliation: Department of Biology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Edidin
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
authors.affiliation: Departments of Pathology, Oncology, and Medicine. Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: jschnec1@jhmi.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schneck
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D007505:Iron-Dextran Complex / Q000276:immunology / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D045663:Quantum Dots / Q000008:administration & dosage / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D007505:Iron-Dextran Complex
keywords: Artificial antigen presenting cell; Immunotherapy; Nanoparticle; T cell
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