Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules

Mol Ther. 2007 May;15(5):981-8. doi: 10.1038/ Epub 2007 Mar 20.


To facilitate the therapeutic application of antigen-presenting cells (APCs), we have developed a cell-based artificial APC (aAPC) system by engineering K562 cells with lentiviruses to direct the stable expression and secretion of a variety of co-stimulatory molecules and cytokines. Here we report the use of a combinatorial lentiviral gene transfer approach to achieve long-term stable expression of at least seven genes in the K562 parental cell line. Expression of various combinations of genes on the aAPC enables the precise determination of human T-cell activation requirements, such that aAPCs can be tailored for the optimal propagation of T-cell subsets with specific growth requirements and distinct functions. The aAPCs support ex vivo growth and long-term expansion of functional human CD8 T cells without requiring the addition of exogenous cytokines, in contrast to the use of natural APCs. Distinct populations of T cells can be expanded with aAPCs expressing CD137L (4-1BBL) and/or CD80. Finally, the aAPCs provide an efficient platform to expand genetically modified T cells and to maintain CD28 expression on CD8 T cells. Therefore, K562-based aAPCs have therapeutic potential for adoptive immunotherapies and vaccinations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism*
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Humans
  • K562 Cells
  • Lentivirus / genetics
  • Microscopy, Phase-Contrast
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism
  • Transduction, Genetic
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism


  • Antigens, Surface
  • CD28 Antigens
  • Cytokines
  • Receptors, IgG
  • Tumor Necrosis Factor Receptor Superfamily, Member 9