Submitted September 19, 2007
Accepted December 16, 2007
Killer-artificial-antigen-presenting-cells (KaAPC):
a novel strategy to delete specific T cells
Christian Schutz*, Martin Fleck, Andreas Mackensen, Alessia Zoso, Dagmar Halbritter, Jonathan P. Schneck, and Mathias Oelke
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
Department of Internal Medicien V, University of Erlangen-Nuernberg, Regensburg, Germany
UM/sylvester comprehensive Cancer Center, Leonard M. Miller School of Medicine, Miami, FL, United States
Department of Pathology, Division of Immunopathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
* Corresponding author; email: christian.schuetz{at}klinik.uni-r.de.
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 (APC). However, APC 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 Antigen Presenting Cells (KaAPC) by coupling an apoptosis-inducing 
-Fas (CD95)-IgM mAb together with HLA-A2-Ig molecules onto beads. These KaAPC deplete targeted antigen-specific T cells in a Fas/FasL dependent fashion. T cell depletion in co-cultures is rapidly initiated (30 min), dependent on the amount of KaAPC and independent of AICD. KaAPC 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.
