摘要:
The invention provides for methods for identification of biologically active biomolecules. In one aspect, a biologically active biomolecule such as RNA or a peptide is identified by incorporating random nucleotide sequences in a scaffold constituted by an enzyme activity modulator, transforming substantially identical host cells with the construct obtained thereby and screening the transformed cells to identify those where a preselected phenotypic trait has been altered. The randomized DNA is subsequently isolated from the phenotypically altered cells and the peptide and/or RNA encoded by the random sequence is determined. In turn, interaction partners which are putative drug targets are identified and isolated by use of the peptide and/or RNA as part of affinity reagents. A preferred scaffold is derived from the potato inhibitor I family of protease inhibitors and exemplified is the barley chymotrypsin inhibitor 2A (CI-2A). Another aspect relates to the identification of novel enzyme inhibitors by using substantially the same approach, but screening specifically for changes in target enzyme activity. Also disclosed are methods of producing the relevant transformation and expression vectors as well as methods for identifying lead compounds and drug targets for use in drug development. Finally, the invention also includes within its scope a method for the preparation of a medicinal product.
摘要:
A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.
摘要:
An increasingly aged population and better diagnosis has lead to an apparent increase in the prevalence of prostate cancer in men. There is an acute need to better understand the progression of this disease from its locally confined site of initiation to the end stage widely metastatic disease with attendant morbidity and mortality. It has historically been difficult to raise and maintain immortalised prostate cell lines in culture. We have derived a cell line selected from the group consisting of clones ONYCAP 1 and ONYCAP23. The cell lines are characterised as being prostate epithelial in origin.
摘要:
A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells aer disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.
摘要:
The invention provides a novel method for down-regulating the biological activity of osteoprotegerin ligand (OPGL, TRANCE) thereby rendering possible the treatment/amelioration of diseases characterized by excessive loss of bone mass, e.g. osteoporosis. Down-regulation is effected by inducing an immune response against OPGL in an individual in need thereof. Immune responses can be raised by classical immunization with immunogenic variants of OPGL or by nucleic acid immunization where the nucleic acids encode the OPGL variant. The invention also pertains to compositions, polypeptides and nucleic acids useful in the invention, as well as to vectors and transformed host cells useful in the preparation thereof.
摘要:
A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.
摘要:
The present invention discloses methods for immunizing against autologous (self) Immunoglobulin E (IgE). In particular, the invention discloses methods for inducing cytotoxic T-lymphocytes that will specifically down-regulate B-cells producing autologous IgE, notably by means of nucleic acid vaccination or live vaccination. Also disclosed are methods for inducing antibodies reactive with autologous IgE as well as methods for inducing a combined antibody and CTK response specific for IgE. The invention also discloses specific immunogenic protein constructs, nucleic acids encoding these as well as various formulations and tools for preparing the vaccines, including vectors and transformed host cells.
摘要:
Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.