Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB

Nat Biotechnol. 2002 Feb;20(2):143-8. doi: 10.1038/nbt0202-143.


The ex vivo priming and expansion of human cytotoxic T lymphocytes (CTLs) has potential for use in immunotherapy applications for cancer and infectious diseases. To overcome the difficulty in obtaining sufficient numbers of CTLs, we have developed artificial antigen-presenting cells (aAPCs) expressing ligands for the T-cell receptor (TCR) and the CD28 and 4-1BB co-stimulatory surface molecules. These aAPCs reproducibly activate and rapidly expand polyclonal or antigen-specific CD8(+) T cells. The starting repertoire of CD8+ T cells was preserved during culture. Furthermore, apoptosis of cultured CD8(+) T cells was diminished by this approach. This approach may have important therapeutic implications for adoptive immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Antigens, CD
  • Apoptosis
  • CD28 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Cell Separation
  • Cells, Cultured
  • Coculture Techniques
  • Flow Cytometry
  • Humans
  • Immunotherapy, Adoptive / methods
  • K562 Cells
  • Ligands
  • Protein Binding
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Time Factors
  • Tumor Necrosis Factor Receptor Superfamily, Member 9


  • Antigens, CD
  • CD28 Antigens
  • Ligands
  • Receptors, Antigen, T-Cell
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF9 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9