{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T23:24:48Z","timestamp":1715988288186},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,24]],"date-time":"2006-01-24T00:00:00Z","timestamp":1138060800000},"content-version":"vor","delay-in-days":876,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>:<\/jats:bold>Although treatment of MG with general immunosuppressive agents is often effective, it has important drawbacks, including suppression of the immune system as a whole, with the risks of infection and neoplasia, and numerous other adverse side effects. Ideally, treatment of MG should eliminate the specific pathogenic autoimmune response to AChR, without otherwise suppressing the immune system or producing other adverse side effects. Although antibodies to AChR are directly responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR antibody response is T cell\u2010dependent, and immunotherapy directed at T cells can abrogate the autoantibody response, with resulting benefit. As in other autoimmune diseases, the T cell response in MG is highly heterogeneous. The design of specific immunotherapy must take this heterogeneity into account and target the entire repertoire of AChR\u2010specific T cells. We describe our investigation of a novel strategy for specific immunotherapy of MG, involving gene transfer to convert antigen\u2010presenting cells (APCs) to \u201cguided missiles\u201d that target AChR\u2010specific T cells, and that induce apoptosis and elimination of those T cells. This strategy uses the ability of APCs from a given individual to present the entire spectrum of AChR epitopes unique for that individual, and thereby to target the entire repertoire of antigen\u2010specific T cells of the same individual. Using viral vectors, we have genetically engineered the APCs to process and present the most important domain of the AChR molecule, and to express a \u201cwarhead\u201d of Fas ligand (FasL) to eliminate the activated AChR\u2010specific T cells with which they interact. Our results show that the APCs express the appropriate gene products, and effectively and specifically eliminate AChR\u2010specific T cells by the Fas\/FasL pathway, while sparing T cells of other specificities.<\/jats:p>","DOI":"10.1196\/annals.1254.068","type":"journal-article","created":{"date-parts":[[2004,1,15]],"date-time":"2004-01-15T01:04:15Z","timestamp":1074128655000},"page":"520-532","source":"Crossref","is-referenced-by-count":10,"title":["Specific Immunotherapy of Experimental Myasthenia by Genetically Engineered APCs"],"prefix":"10.1111","volume":"998","author":[{"given":"D. B.","family":"DRACHMAN","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u2010M.","family":"WU","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"MIAGKOV","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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