title: Polymer nanoparticles containing tumor lysates as antigen delivery vehicles for dendritic cell-based antitumor immunotherapy.
abstract: Encapsulation of tumor-associated antigens in polymer nanoparticles (NP) is a promising approach to enhance efficiency of antigen delivery for anti-tumor vaccines. Head and neck squamous carcinoma (HNSCC) cell lines were initially used to generate tumor-associated antigens (TAA)-containing poly (lactic-co-glycolic acid) (PLGA) NP; encapsulation efficiency and release kinetics were profiled. Findings were adopted to entrap fresh tumor lysate from five patients with advanced HNSCC. To test the hypothesis that NP enhance antigen presentation, dendritic cell (DC) produced from patient blood monocyte precursors were loaded with either the un-encapsulated or NP-encapsulated versions of tumor lysates. These were used to stimulate freshly-isolated autologous CD8+ T cells. In four of five patients, anti-tumor CD8+ T cells showed significantly increased immunostimulatory IFN-γ (p=0.071) or decreased immmunoinhibitory IL-10 production (p=0.0004) associated with NP-mediated antigen delivery. The observations represent an enabling step in the production of clinically-translatable, inexpensive, highly-efficient, and personalized polymer-based immunotherapy for solid organ malignancies.
  
  
  BACKGROUND
  Enhancing the antigen presentation may be a viable approach to increase the efficiency of tumor cell directed cytotoxicity via immune mechanisms. This study presents an example for this using head and neck cancer cell lines and nanotechnology-based encapsulated antigen presentation to dendritic cells. The observed CD8+ T-cell response was significantly enhanced. This method may pave the way to a highly efficient cancer cell elimination method with minimal to no toxicity.
authors.affiliation: Department of Dermatology, Yale University, New Haven, Connecticut, USA.
authors.forename: Shashi
authors.initials: S
authors.lastname: Prasad
authors.forename: Virginia
authors.initials: V
authors.lastname: Cody
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Saucier-Sawyer
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.forename: Clarence T
authors.initials: CT
authors.lastname: Sasaki
authors.forename: Richard L
authors.initials: RL
authors.lastname: Edelson
authors.forename: Martin A
authors.initials: MA
authors.lastname: Birchall
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hanlon
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000628:therapy*; D011108:Polymers / Q000737:chemistry*
chemical_list: D011108:Polymers