Research Experience and Subjects:
IMMUNOLOGY / DENDRITIC CELLS (DC)
Dendritic Cells (DC) are leukocytes specialized to initiate immune responses. DC were ignored over many years following their discovery by R.M. Steinman and Z. Cohn but are now in the focus of immunological research due to their role in T cell-mediated immunity and clinical immunology (immunity to tumors, resistance to infections, allergy, pathogenesis of HIV-infection, transplantation, tolerance and autoimmunity). We have been working for several years to elucidate the biology of these cells and have developed methods to generate DC from hematopoietic precursors (patents pending).
This knowledge is now employed to adress a number of issues:
- Use of antigen-charged DC for immunotherapy of malignant melanoma and HIV-infection (two clinical trials have been finished, several ones are under way)
- Identification of novel DC-restricted molecules by molecular biology approaches
Induction of tolerance using DC
- Allergy, notably to drugs and latex
MALIGNANT MELANOMA
We are exploring novel approaches employing antigen-charged dendritic cells to induce immunity in vivo (see above).
Selected References:
Schuler G, Steinman RM
Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro.
J. Exp. Med. 161:526,1985.
Heufler C, Koch F, Schuler G
Granulocyte-macrophage colony-stimulating factor and interleukin-1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells.
J. Exp. Med. 167:700,1988.
Kämpgen E, Koch F, Heufler C, Eggert A, Gill LL, Gillis S, Dower SK, Romani N, Schuler G
Understanding the dendritic cell lineage through a study of cytokine receptors.
J. Exp. Med. 179:1767,1994.
Inaba K, Steinman RM, Pack MW, Aya H, Inaba M, SudoT, Wolpe S, Schuler G.
Identification of proliferating dendritic cell precursors in mouse blood.
J. Exp. Med. 175:1157,1992.
Romani N, Gruner S, Brang D, Kämpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G
Proliferating dendritic cell progenitors in human blood.
J. Exp. Med. 180:83,1994.
Romani N, Reider D, Heuer M, Ebner S, Eibl B, Niederwieser D, Kämpgen E, Schuler G
Generation of mature dendritic cells from human blood: an improved method with special regard to clinical applicability.
J. Immunological Methods 196: 137,1996.
Lenz A, Heine M, Schuler G, Romani N.
Human and murine dermis contain dendritic cells.
J. Clin. Invest. 92:2587,1993.
Heufler C, Koch F, Stanzl U, Topar G, Wysocka M, Trichieri G, Enk A, Steinman RM, Romani N, Schuler G.
Interleukin-12 is produced by DC and mediates Th1 development as well as IFN gamma production by Th1 cells.
Eur. J. Immunol.26: 659,1996.
Koch F, Stanzl U, Jennewein P, Janke K, Heufler C, Kämpgen E, Romani N, Schuler G
High level IL-12 production by murine dendritic cells: Upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
J. Exp. Med. 184:741,1996.
Eibl B, Ebner S, Duba C, Böck G, Romani N, Erdel M, Gächter A, Niederwieser D, Schuler G
Dendritic cells generated from blood precursors of chronic myelogenous leukemia patients carry the Philadelphia translocation and can induce a CML-specific primary cytotoxic T-cell response.
Genes, Cromosomes & Cancer 20: 215-223, 1997.
Thurner B, Röder C, Dieckmann D, Heuer M, Kruse M, Glaser A, Kämpgen E, Bender A, Schuler G
Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical appplication.
J. Immunol. Methods 223: 1-15, 1999.
Thurner B, Haendle I, Röder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, Bröcker EB, Steinman RM, Enk A, Kämpgen E, Schuler G
Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma.
J. Exp. Med. 190: 1669-1678, 1999.
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