title: Artificial antigen-presenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8+ CD28+ T lymphocyte responses.
abstract: OBJECTIVE
  To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8(+) CD28(+) cytotoxic T lymphocyte (CTL) responses.
  
  
  METHODS
  Cell-sized Dynabeads® M-450 Epoxy beads coated with H-2K(b): Ig-TRP2180-188 and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8(+)CD28(+) CTL responses with the help of IL-21 and IL-15. Dimer staining, proliferation, ELISPOT, and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.
  
  
  RESULTS
  Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8(+)CD28(+)CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- γ under the stimulation of H-2K(b): Ig-TRP2-aAPCs, IL-15, and IL-21. In addition, cytotoxicity experiments showed that induced CTLs have specific killing activity of target cells.
  
  
  CONCLUSIONS
  The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8(+) CD28(+) CTLs against the melanoma. Our study provides evidence for a novel adoptive immunotherapy against tumors.
authors.affiliation: Biological Targeting Diagonosis and Therapy Research Center, Guangxi Medical University, Nanning, Guangxi 530021, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Sodaly
authors.initials: S
authors.lastname: Mongkhoune
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Zhou
authors.forename: Xiao-Xun
authors.initials: XX
authors.lastname: Xie
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Luo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Nuo
authors.initials: N
authors.lastname: Zhou
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Zhao
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Lu
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D058045:Artificial Cells / Q000737:chemistry / Q000276:immunology*; D018106:CD28 Antigens / Q000737:chemistry / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007378:Interleukins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D018106:CD28 Antigens; D004337:Drug Carriers; D019409:Interleukin-15; D007378:Interleukins; D008565:Membrane Proteins; D010446:Peptide Fragments; C500290:peptide SVYDFFVWL; D007371:Interferon-gamma; D000098546:Interleukin-21