Novel Method for Rapidly Generating Mature Dendritic Cells from Peripheral Blood Monocytes and Myeloid Precursors
This application claims use of CpG oligodeoxynucleotides (ODN) to generate mature dendritic cells (DC). Also claimed in the application are synergistic uses of CpG ODNs with cytokines, chemokines, or other factors to induce the maturation of monocytes to dendritic cells. Dendritic cells play a critical role in the generation of adaptive immune responses. Dendritic cells excel at presenting antigen to naive T lymphocytes. Large numbers of highly active DC are necessary for prevention and/or treatment of cancer and infectious diseases. Current processes for generating mature DC from peripheral blood mononuclear cells (PBMC) involve incubating PBMC with GM-CSF plus IL-4 for one week followed by monocyte-conditioned medium for two to seven days. These processes are inefficient, expensive and do not uniformly generate DC with full functional activity. The current invention is based on the observation that bacterial DNA and synthetic ODNs containing unmethylated "CpG motifs" promote the maturation of murine antigen presenting cells (APC) in vitro.
The invention is further described in Ishii KJ et al., "Genomic DNA released by dying cells induces the maturation of APCs," J. Immunol. 2001 Sep 1;167(5):2602-7.
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
10903 New Hampshire Ave.
Building WO1, Rm 4214
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OTT Reference No: E-214-2001/0
Updated: August 10, 2015