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Cutting Edge: Predetermined Avidity of Human CD8 T Cells Expanded on Calibrated MHC/Anti-CD28-Coated Microspheres ¹

Steffen Walter^*, Leah Herrgen^*, Oliver Schoor^*, Gundram Jung^*, Dorothee Wernet, Hans-Jörg Bühring, Hans-Georg Rammensee^* and Stefan Stevanovi^2,*

^* Department of Immunology, Institute for Cell Biology, Department of Transfusion Medicine, and Department of Internal Medicine II, Division of Hematology and Oncology, University of Tübingen, Tübingen, Germany

Cytotoxic CD8 T cells are key effectors in the immunotherapy of malignant and viral diseases. However, the lack of efficient methods for their in vitro priming and expansion has become a bottleneck to the development of vaccines and adoptive transfer strategies. Synthetic artificial APCs (aAPCs) are now emerging as an attractive tool for eliciting and expanding CTL responses. We show that, by controlling the MHC density on aAPCs, high- or low-avidity tumor-directed human CTL lines can be raised effectively in vitro if costimulation via CD28 and IL-12 is provided. Compared with low-avidity CTL lines, high-avidity CTLs need 100- to 1000-fold less peptide for activation, bind more MHC tetramers, and, as expected, are superior in recognizing tumor cell lines expressing Ag. We believe that the possibility to raise Ag-specific T cells with predetermined avidity will be crucial for the future use of aAPCs in immunotherapeutical settings.

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