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 Blood, 1 April 2008, Vol. 111, No. 7, pp. 3546-3552.
Prepublished online as a Blood First Edition Paper on December 20, 2007; DOI 10.1182/blood-2007-09-113522.

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IMMUNOBIOLOGY

Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells

Christian Schütz1,2, Martin Fleck1, Andreas Mackensen3,4, Alessia Zoso2,5, Dagmar Halbritter1, Jonathan P. Schneck1, and Mathias Oelke1

1 Department of Internal Medicine I, University of Regensburg, Regensburg, Germany; 2 Division of Immunopathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; 3 Division of Hematology and Oncology, University of Regensburg, Regensburg, Germany; 4 Department of Internal Medicine V, University of Erlangen-Nuernberg, Erlangen, Germany; and 5 Leonard M. Miller School of Medicine, University of Miami/Sylvester Comprehensive Cancer Center, FL

Several cell-based immunotherapy strategies have been developed to specifically modulate T cell–mediated immune responses. These methods frequently rely on the utilization of tolerogenic cell–based antigen-presenting cells (APCs). However, APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their therapeutic capacity. Here, we describe a novel bead-based approach to modulate T-cell responses in an antigen-specific fashion. We have generated killer artificial APCs ({kappa}aAPCs) by coupling an apoptosis-inducing {alpha}-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These {kappa}aAPCs deplete targeted antigen-specific T cells in a Fas/Fas ligand (FasL)–dependent fashion. T-cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the amount of {kappa}aAPCs and independent of activation-induced cell death (AICD). {kappa}aAPCs represent a novel technology that can control T cell–mediated immune responses, and therefore has potential for use in treatment of autoimmune diseases and allograft rejection.


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Related Article in Blood Online:

Killer aAPCs as tools for immunosuppression
Hermann Einsele
Blood 2008 111: 3305. [Full Text] [PDF]





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