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filingDate 1995-08-31-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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publicationDate 1996-03-28-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber WO-9606929-A3
titleOfInvention Rapid expansion method ('rem') for in vitro propagation of t lymphocytes
abstract The present invention provides a rapid expansion method (termed 'REM'), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes. REM involves culturing the T cells in association with a disproportionately large concentration of nondividing feeder cells, preferably η-irradiated peripheral blood mononuclear cells ('PBMC') present at an excess of at least 40-fold (relative to the number of target T cells), more preferably at an excess of at least about 200-fold. Cultures grown under REM exhibit dramatically enhanced expansion rates that can be even further elevated by the use of appropriate concentrations of an additional feeder cell, an anti-CD3 monoclonal antibody and IL-2, as described herein. Clonal expansions in the range of 500-fold to 3000-fold can be achieved within a single stimulation cycle of about 10-13 days, which is more than 100-fold more efficient than currently employed methods of culturing human T cell clones. Genetic transduction efficiencies were also enhanced using REM-expanded T lymphocytes. Several examples involving human bone narrow transplant recipients illustrate the effective use of REM-expanded antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy in humans.
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