title: Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy.
abstract: Adoptive immunotherapy (AIT) can mediate durable regression of cancer, but widespread adoption of AIT is limited by the cost and complexity of generating tumor-specific T cells. Here we develop an Enrichment + Expansion strategy using paramagnetic, nanoscale artificial antigen presenting cells (aAPC) to rapidly expand tumor-specific T cells from rare naïve precursors and predicted neo-epitope responses. Nano-aAPC are capable of enriching rare tumor-specific T cells in a magnetic column and subsequently activating them to induce proliferation. Enrichment + Expansion resulted in greater than 1000-fold expansion of both mouse and human tumor-specific T cells in 1 week, with nano-aAPC based enrichment conferring a proliferation advantage during both in vitro culture and after adoptive transfer in vivo. Robust T cell responses were seen not only for shared tumor antigens, but also for computationally predicted neo-epitopes. Streamlining the rapid generation of large numbers of tumor-specific T cells in a cost-effective fashion through Enrichment + Expansion can be a powerful tool for immunotherapy.
authors.forename: Karlo
authors.initials: K
authors.lastname: Perica
authors.forename: Joan Glick
authors.initials: JG
authors.lastname: Bieler
authors.forename: Christian
authors.initials: C
authors.lastname: Schütz
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Varela
authors.affiliation: ∥Ludwig Cancer Research Center and Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Douglass
authors.affiliation: ∥Ludwig Cancer Research Center and Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Skora
authors.forename: Yen Ling
authors.initials: YL
authors.lastname: Chiu
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
authors.affiliation: ∥Ludwig Cancer Research Center and Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kinzler
authors.affiliation: ∥Ludwig Cancer Research Center and Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhou
authors.affiliation: ∥Ludwig Cancer Research Center and Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schneck
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000951:Antigens, Neoplasm
keywords: adoptive immunotherapy; immunotherapy; nanoparticles