Killer Artificial Antigen-Presenting Cells: The Synthetic Embodiment of a ‘Guided Missile‘

Abstract

At present, the treatment of T-cell-dependent autoimmune diseases relies exclusively on strategies leading to nonspecific suppression of the immune systems causing a substantial reduced ability to control concomitant infections or malignancies. Furthermore, long-term treatment with most drugs is accompanied by several serious adverse effects and does not consequently result in cure of the primary immunological malfunction. By contrast, antigen-specific immunotherapy offers the potential to achieve the highest therapeutic efficiency in accordance with minimal adverse effects. Therefore, several studies have been performed utilizing antigen-presenting cells specifically engineered to deplete allo- or antigen-specific T cells (‘guided missiles‘). Many of these strategies take advantage of the Fas/Fas ligand signaling pathway to efficiently induce antigen-presenting cell-mediated apoptosis in targeted T cells. In this article, we discuss the advantages and shortcomings of a novel non-cell-based ‘killer artificial antigen-presenting cell‘ strategy, developed to overcome obstacles related to current cell-based approaches for the treatment of T-cell-mediated autoimmunity.

KEYWORDS::

• antigen-presenting cell
• apoptosis
• artificial
• killer artificial antigen-presenting cell
• T cell

Financial & competing interests disclosure

Primary work on killer artificial antigen-presenting cells was supported in parts by Deutsche Forschungsgemeinschaft KFO146 (to Andreas Mackensen and Martin Fleck), Wilhelm Sander Stiftung (to Martin Fleck), Department of Defense grant PC 040972 (to Mathias Oelke) and NIH grants RO1 CA108835, RO1 AI44129, ROI AI29575 and ROI AI072677 (to Jonathan P Schneck). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Primary work on killer artificial antigen-presenting cells was supported in parts by Deutsche Forschungsgemeinschaft KFO146 (to Andreas Mackensen and Martin Fleck), Wilhelm Sander Stiftung (to Martin Fleck), Department of Defense grant PC 040972 (to Mathias Oelke) and NIH grants RO1 CA108835, RO1 AI44129, ROI AI29575 and ROI AI072677 (to Jonathan P Schneck). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.