| 摘要 |
#CMT# #/CMT# Preparing effective dendritic cells or cell lines (A) comprising treating cells (B) of CD124- and CD116-positive lines with at least one stimulatory molecule (I), applied at the same time or sequentially, is new. #CMT# : #/CMT# Independent claims are also included for the following: (1) preparing a pharmaceutical composition by producing (A) by the new method then formulating with carrier and optionally an adjuvant; (2) kit or test system containing (A); and (3) test system comprising (i) CD124- and CD116-positive or (ii) MUTZ-3 cells. #CMT#ACTIVITY : #/CMT# Cytostatic; Antirheumatic; Immunosuppressive; Immunostimulatory; Antibacterial; Virucide; Antiparasitic; Fungicide; Dermatological; Antiinflammatory; Antianemic; Nephrotropic; Thyrotropic; Antidiabetic; Anthelmintic; Protozoacide. No biological data given. #CMT#MECHANISM OF ACTION : #/CMT# Vaccine; Immunotherapy. #CMT#USE : #/CMT# (A) are useful: (a) as (semi)allogenic immunotherapeutic agents; (b) for activating, inhibiting or modulating the humoral and/or cellular immune systems; (c) for stimulating natural killer, CD4+ and/or cytotoxic T cells; (d) for processing and presenting antigens; and (e) to induce proliferation of immune cells. Particularly they are used to treat or prevent, as vaccines, infections (by viruses, bacteria, parasites, protozoa, prions or helminths), tumors and/or autoimmune diseases (e.g. anemia; Hashimoto's syndrome; insulin-dependent diabetes; rheumatism; systemic lupus erythematosus; Goodpasture syndrome and many others listed); also in transplantation medicine and for diagnosis. Systems containing (A) are also useful for testing the immuno-activating, -inhibiting and/or -modulating activities of substances and/or for analyzing the biology of dendritic cells. #CMT#BIOLOGY : #/CMT# Preferred Cells: (A) are equivalent, or similar, phenotypically to interstitial, Langerhans or (im)mature dendritic cells, or CD83-positive cells. (B) are also CD34-positive and are obtained from tumor or primary cells, especially by incorporation of genes for the various CD proteins. Most preferably the cells are obtained from patients with chronic or acute myeloid leukemia and are of myeloid, lymphoid, plasmocytoid or monocytic origins. The cells may include additional genes, e.g. encoding for receptors or inhibitors of stimulatory molecules, or an immunotherapeutic gene, and they may be fused with other cells or cell lines. Many suitable (B) are specified; most preferred is MUTZ-3. Preferred Materials: (I) is a molecule that modifies cell differentiation, e.g. a cytokine or co-stimulatory molecule such as granulocyte-macrophage colony-stimulating factor; tumor necrosis factor alpha , lipopolysaccharide; prostaglandin E2; CD40 ligand or calcium; or a surrogate, e.g. antibody or peptide. (I) may induce differentiation and/or maturation. Preferred Process: (A) with different stages of activation and/or effector status can be produced by varying the nature, dose and/or timing of tretament with (I). (A) or (B) may be rendered apoptotic or necrotic, e.g. by irradiation and/or introduction of a suicide gene. For therapeutic use, (A) are: (a) loaded with one or more tumor or pathogen antigens or their fragments, or with tumor (or infected) cell lysate; (b) fused to tumor (or infected) cells; or (c) modified with a gene that encodes a tumor, viral, bacterial or parasite antigen, or other genes that encode an infectious paricle. #CMT#WIDER DISCLOSURE : #/CMT# Disclosed is a method for identifying peptides that are presented by (A) comprising: (a) treating (A) with antigens, immunogens or cell lysates, so that (A) mature; (b) isolating presented peptides from mature cells; and (c) determining their identities. #CMT#ADMINISTRATION : #/CMT# (A) are administered by injection or mucosally, optionally with additional immunostimulatory substances such as cytokines, typically at doses of 100-10 12>, particularly 10 6>-10 10>, cells. #CMT#EXAMPLE : #/CMT# The human leukemic MUTZ-3 (CD34+, CD116+ and CD124+) cell line was incubated with 100 ng/ml of granulocyte-macrophage colony-stimulating factor; 1000 units/ml interleukin-4 and 2.5 ng/ml tumor necrosis factoralpha (X) for 7 days. 20% of the cells were then positive for CD1a, a characteristic of immature dendritic cells (DC). Conversion to mature DC was induced in presence of 75 ng/ml (X) and 100 ng/ml of lipopolysaccharide. The mature DC were able, in a mixed lymphocyte reaction, to stimulate proliferation of T cells, with incorporation of tritium 6-10 times greater than for unstimulated MUTZ-3 cells, and 2-3 times greater than for immature MUTZ-3 DC. |
