The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells. Academic Article uri icon



  • BACKGROUND: Adoptive cell therapy with ex vivo expanded autologous antitumor cytotoxic T lymphocytes represents an important therapeutic option as an anticancer strategy. In order to identify a reliable method for producing adequate amounts of functional antitumor cytotoxic T lymphocytes with a potentially long in vivo lifespan, we tested the T-cell expansion efficiency of a new artificial antigen-presenting cell-based system. DESIGN AND METHODS: Our artificial antigen-presenting cells were generated with activating (anti-CD3), co-stimulating (anti-CD28) and adhesion (anti-LFA-1) biotinylated monoclonal antibodies preclustered in microdomains held on a liposome scaffold by neutravidin rafts. The co-localization of T-cell ligands in microdomains and the targeting of an adhesion protein, increasing the efficiency of immunological synapse formation, represent the novelties of our system. The activity of our artificial antigen-presenting cells was compared with that of anti-CD3/-CD28 coated immunomagnetic microbeads and immobilized anti-CD3 monoclonal antibody (OKT3 clone), the only two commercially available artificial systems. RESULTS: Our artificial antigen-presenting cells expanded both polyclonal T cells and MART-1-specific CD8(+) T cells in a more efficient manner than the other systems. Stimulation with artificial antigen-presenting cells allows for the generation of viable T cells displaying an immunophenotype consistent with in vivo potential for persistence, without increasing the frequency of regulatory T cells. The starting specificity of anti MART-1 CD8(+) T cells was preserved after stimulation with artificial antigen-presenting cells and it was statistically greater when compared to the activity of the same cells expanded with the other systems. Finally, our artificial antigen-presenting cells proved to be suitable for large-scale application, minimizing the volume and the costs of T-cell expansion. CONCLUSIONS: Our artificial antigen-presenting cells might represent an efficient tool to rapidly obtain a sufficient number of functional T cells for adoptive immunotherapy in patients with cancer.


  • Zappasodi, Roberta
  • Di Nicola, Massimo
  • Carlo-Stella, Carmelo
  • Mortarini, Roberta
  • Molla, Alessandra
  • Vegetti, Claudia
  • Albani, Salvatore
  • Anichini, Andrea
  • Gianni, Alessandro M

publication date

  • August 25, 2008



  • Antibodies, Monoclonal
  • Antigen-Presenting Cells
  • CD28 Antigens
  • CD3 Complex
  • Lymphocyte Function-Associated Antigen-1
  • Neoplasms
  • T-Lymphocytes


Scopus Document Identifier

  • 54349104900

Digital Object Identifier (DOI)

  • 10.3324/haematol.12521

PubMed ID

  • 18728033

Additional Document Info


  • 93


  • 10