title: A novel system of artificial antigen-presenting cells efficiently stimulates Flu peptide-specific cytotoxic T cells in vitro.
abstract: Therapeutic numbers of antigen-specific cytotoxic T lymphocytes (CTLs) are key effectors in successful adoptive immunotherapy. However, efficient and reproducible methods to meet the qualification remain poor. To address this issue, we designed the artificial antigen-presenting cell (aAPC) system based on poly(lactic-co-glycolic acid) (PLGA). A modified emulsion method was used for the preparation of PLGA particles encapsulating interleukin-2 (IL-2). Biotinylated molecular ligands for recognition and co-stimulation of T cells were attached to the particle surface through the binding of avidin-biotin. These formed the aAPC system. The function of aAPCs in the proliferation of specific CTLs against human Flu antigen was detected by enzyme-linked immunospot assay (ELISPOT) and MTT staining methods. Finally, we successfully prepared this suitable aAPC system. The results show that IL-2 is released from aAPCs in a sustained manner over 30 days. This dramatically improves the stimulatory capacity of this system as compared to the effect of exogenous addition of cytokine. In addition, our aAPCs promote the proliferation of Flu antigen-specific CTLs more effectively than the autologous cellular APCs. Here, this aAPC platform is proved to be suitable for expansion of human antigen-specific T cells.
authors.affiliation: Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Han
authors.forename: Ji-Run
authors.initials: JR
authors.lastname: Peng
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.forename: Shi-Shi
authors.initials: SS
authors.lastname: Qiao
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Wang
authors.forename: Zhu-Qingqing
authors.initials: ZQ
authors.lastname: Cui
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Wei
authors.forename: Xi-Sheng
authors.initials: XS
authors.lastname: Leng
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D058045:Artificial Cells / Q000276:immunology*; D001360:Avidin / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D019921:Biotinylation; D002214:Capsules; D058501:Enzyme-Linked Immunospot Assay; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000737:chemistry / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry; D008024:Ligands; D008213:Lymphocyte Activation; D008863:Microspheres; D010446:Peptide Fragments / Q000276:immunology*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D002214:Capsules; D007376:Interleukin-2; D008024:Ligands; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); D001360:Avidin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001710:Biotin