Abstract:
The present invention provides recombinant CEA glycoproteins and methods for their production. These recombinant CEA glycoproteins s lack the C-terminal 26 amino acids which are present in natural CEA and are characterized in that they are free from cross-reactive CEA-like antigens, antigenically indistingiushable from the soluble form of CEA shed from tumor cells, and devoid of the ethanolamine which is present at the C-terminus of natural CEA, and also devoid of the additional amino acids which may be attached to the natural CEA through said ethanolamine. Said recombinant CEA glycoproteins s preferably have the amino acid sequence SEQ ID NO: 1. The CEA glycoproteins s of the invention may be used as reagents in an immunoassay for the diagnosis of neoplastic diseases. The invention also relates to a DNA encoding said recombinant CEA glycoprotein, such as the DNA having the nucleotide sequence SEQ ID NO: 2 or a functional equivalent sequence thereof. The present invention also relates to recombinant vectors comprising said DNA, which recombinant vector is capable of directing the expression of said DNA in a compatible host cell, and to transformed host cells containing such a recombinant vector. The recombinant CEA glycoprotein of the present invention, preferably integrated in a test-kit, may be used for determining the presence of tumor cells in a sample of body fluid.
Abstract translation:本发明提供重组CEA糖蛋白及其生产方法。 这些重组CEA糖蛋白缺乏存在于天然CEA中的C-末端26个氨基酸,其特征在于它们不具有从可溶形式从肿瘤细胞中流出的CEA抗原性不可抵抗的交叉反应性CEA-样抗原,以及 没有存在于天然CEA的C末端的乙醇胺,也没有可以通过所述乙醇胺与天然CEA连接的另外的氨基酸。 所述重组CEA糖蛋白优选具有SEQ ID NO:1的氨基酸序列。本发明的CEA糖蛋白可用作用于诊断肿瘤疾病的免疫测定中的试剂。 本发明还涉及编码所述重组CEA糖蛋白的DNA,例如具有核苷酸序列SEQ ID NO:2的DNA或其功能等同序列。 本发明还涉及包含所述DNA的重组载体,所述重组载体能够引导所述DNA在相容宿主细胞中的表达,以及含有这种重组载体的转化宿主细胞。 优选整合在试验盒中的本发明的重组CEA糖蛋白可用于测定体液样品中肿瘤细胞的存在。
Abstract:
The present invention concerns an oligomer comprising more than 2 units, wherein each unit comprises a peptidic domain capable of oligomerizing and a domain capable of binding to an acceptor (ligand), wherein the oligomerizing domain is not an antibody or a functional antibody fragment from the constant region. Also described is the use and synthesis of this oligomer.
Abstract:
The invention is directed to a compound comprising one or more CD1d complexes in association with an antibody specific for a cell surface marker. The CD1d complexes comprise a CD1d, a β2-microglobulin molecule, and may further comprise an antigen bound to the CD1d binding groove. The invention is further directed to methods of inhibiting or stimulating an immune response with the CD1d-antibody compounds, in particular anti-tumor and autoimmunity responses.
Abstract:
The present invention relates to a pharmaceutical composition representing a novel immunomodulating principle comprising bacterial endotoxin, fetal hemoglobin or more particularly a heme-free derivative or the γ-chain thereof, and optionally, components which are present in the fetal liver in addition to HbF. The composition is delivered to humans in a pharmaceutically acceptable carrier and/or diluent. In accordance with the present invention it was surprisingly found that endotoxin and fetal hemoglobin partial structures display a pronounced synergistic biomedical activity. The biomedical effect of fetal hemoglobin and its partial structures is surprisingly not based on a classical hemoglobin function as an oxygen transporter but related to a modulation of endotoxin-mediated bioactivity. This biomedical activity is surprisingly also observed after oral application of the composition. The composition of the invention finds a variety of applications which have in common the stimulation of the immune system and the reversion in polarization of cytokines and chemokines from a Th2-directed response to a Th1-type response. The proposed applications would therefore include the treatment of allergic conditions, malignancies, chronic infections, autoimmune phenomena and age-related imbalances.
Abstract:
The invention relates to multispecific antibody constructs comprising Fab fragments having mutations at the interface of the CH1 and CL domains, said mutations preventing heavy/light chain mispairing.
Abstract:
The present invention relates to a pharmaceutical composition representing a novel immunomodulating principle comprising bacterial endotoxin, fetal hemoglobin or more particularly a heme-free derivative or the γ-chain thereof, and optionally, components which are present in the fetal liver in addition to HbF. The composition is delivered to humans in a pharmaceutically acceptable carrier and/or diluent. In accordance with the present invention it was surprisingly found that endotoxin and fetal hemoglobin partial structures display a pronounced synergistic biomedical activity. The biomedical effect of fetal hemoglobin and its partial structures is surprisingly not based on a classical hemoglobin function as an oxygen transporter but related to a modulation of endotoxin-mediated bioactivity. This biomedical activity is surprisingly also observed after oral application of the composition. The composition of the invention finds a variety of applications which have in common the stimulation of the immune system and the reversion in polarization of cytokines and chemokines from a Th2-directed response to a Th1-type response. The proposed applications would therefore include the treatment of allergic conditions, malignancies, chronic infections, autoimmune phenomena and age-related imbalances.
Abstract:
The invention concerns novel monoclonal antibodies with high specificity to and affinity for human carcinoembryonic antigen (CEA), derivatives thereof, processes for the preparation of these antibodies and their derivatives, hybridoma cell lines secreting the antibodies, and processes for the preparation of said cell lines. The monoclonal antibodies of the invention and their derivatives are useful in the diagnosis and therapy of cancer and serial monitoring of cancer patients for recurrent disease or response to therapy. Test kits and pharmaceutical compositions containing said monoclonal anti-CEA antibodies are also subject of the invention.
Abstract:
The invention relates to immunoconjugates of formula: A-B—(C)n where B may be present or absent, A is a specific binding protein such as an antibody or an antibody binding fragment, or a ligand binding to a receptor present on target cells B comprises at least one molecule to which “A” and “C” bind, such as an avidin/streptavidin complex, “C” is an MHC molecule, and “n” is a whole number ranging from 1 to 10. The conjugates provide the exquisite binding specificity of antibodies, combined with an ability to stimulate cytotoxic T cells to identify and to destroy cells on which the conjugate is bound and oligomerized. The conjugates are useful both therapeutically and diagnostically.
Abstract:
The present invention relates to an isolated and recombinant fusion peptabody, which binds to a member of the epidermal growth factor receptor useful in inhibiting the growth of certain tumor cells. Also disclosed are, nucleic acids encoding said isolated and recombinant fusion peptabody, kits and pharmaceutical compositions comprising said isolated and recombinant fusion peptabody as an active substance. Finally, a method for the manufacture of said isolated and recombinant fusion peptabody, and its use for the preparation of a medicament for the treatment or prevention of cancer are provided.
Abstract:
The invention is directed to a compound comprising one or more CD1d complexes in association with an antibody specific for a cell surface marker. The CD1d complexes comprise a CD1d, a β2-microglobulin molecule, and may further comprise an antigen bound to the CD1d binding groove. The invention is further directed to methods of inhibiting or stimulating an immune response with the CD1d-antibody compounds, in particular anti-tumor and autoimmunity responses.