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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2397-2402. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-01-0324.
Submitted January 29, 2004
Molecular Pharmacology and Chemistry, Sloan-Kettering Institute and Memorial Sloan-Kettering Cancer Center, New York, NY, USA * Corresponding author; email: d-scheinberg{at}ski.mskcc.org.
Immunosuppressive agents in current use are non-specific. The capacity to delete specific CD8 T cell clones of unique specificity could prove to be a powerful tool for dissecting the precise role of CD8+ T cells in human disease and could form the basis for a safe, highly selective therapy of autoimmune disorders. MHC tetramers (multimeric complexes capable of binding to specific CD8 T cell clones) were conjugated to 225Ac (an alpha emitting atomic nanogenerator, capable of single hit killing from the cell surface) to create an agent for CD8 T cell clonal deletion. The "suicide" tetramers specifically bound to, killed, and reduced the function of their cognate CD8 T cells (either human anti-EBV or mouse anti-Listeria in two model systems) while leaving unharmed, non-specific control CD8 T cell populations. Such an approach may allow a pathway to selective ablation of pathogenic T cell clones ex vivo or in vivo without disturbing general immune function.
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