Abstract: Disclosed are methods of stimulating in a subject an immune response to an antigen to which the immune response is targeted. This method includes the step of administering to the subject a binding agent which binds a surface receptor of an antigen-presenting cell, in some instances without being blocked substantially by the natural ligand for the surface receptor, and an antigen to which the immune response is targeted, in a physiologically acceptable medium to the subject. Also disclosed are molecular complexes including the binding agent coupled to an antigen.

Abstract: The invention features substantially purified polypeptide fragments of two specific domains, namely the ART domain and the transmembrane domain, within the BAX protein which, when administered to a cell, increase or decrease apoptosis of the cell. Also disclosed are methods for identifying compounds which, when administered to a cell, increase or decrease apoptosis of the cell. These compounds are identified based on their abilities to interact with specific domains of the BAX protein, or to alter the interaction of the BAX ART domain with the BAX transmembrane domain. In addition, the invention provides methods for diagnosing a patient having, or predisposed to develop, a disease involving altered apoptosis by identifying a mutation in a BAX-encoding gene which results in an amino acid mutation in the BAX ART domain, a BAX transmembrane domain, or that alters the interaction of the BAX ART domain with the BAX transmembrane domain.

Abstract: Hybridomas secreting monoclonal antibodies specific for an epitope found in the amino acids of LCGA associated with non-small cell lung carcinoma protein have been found. The monoclonal antibodies produced by these hybridomas can be used in in vivo and in vitro clinical diagnosis of non-small cell lung carcinoma and ovarian carcinoma and as target selective carriers for various anti-tumor agents and radioimaging agents.

Abstract: The invention provides a human glutathione peroxidase (GPx6) and polynucleotides which identify and encode GPx6. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of GPx6.

Abstract: A cancer immunogen comprises foreign MHC molecules and additionally one or more oncognes (or constructs that will produce an antigenic region thereof) which can be used to immunize against tumors containing the same or similar oncogenes. Where pathogen-free allogeneic cells are used, it may not be necessary to kill the vaccine before it is administered. The efficacy of the vaccine may be enhanced if the cells also contain immunoenhancing molecules, tumor antigens, or third-party antigens. Cell vaccines containing oncongens can be standardized and used to treat (risk of) specific cancers where there are analogous oncongenes in the tumor or pre-cancerous cells. A panel of such cells covering different oncogenes may be used. The vaccines can be used to immunize prophylactically, in conduction with other therapy, post-surgery or on their own.

Abstract: The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7. The invention also provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a pro-caspase such as pro-caspase-9. In addition, the invention also provides methods for identifying agents that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP.

Abstract: Superantigens, including staphylococcal enterotoxins, are useful agents in the killing of tumor cells, the enhancement of antitumor immunity and in the treatment of cancer in a tumor-bearing host. In particular, the immune system of a subject with cancer is contacted with tumor cells that have been transfected with nucleic acid encoding a superantigen or biologically active polypeptide of a superantigen. Alternatively, transfected accessory cells, immunocytes or fibroblasts are used. When the superantigen is expressed in the host, T cell proliferation is induced leading to increased antitumor immunity and tumor cell killing. The nucleic acid encoding a superantigen may be administered to the tumor in vivo to transfect tumor cells wherein superantigen expression induces a similar tumoricidal immune response.

Abstract: Primary screening for cervical dysplasia is effected by measuring a biochemical marker of apoptosis and/or angiogenesis in each of a population of cells derived from convenient, superficial swabbing, sponging, scraping or lavage of superficial epithelial cells from the cervix, wherein the marker indicates the presence of cervical dysplasia in the sample, and scoring the results of the measuring step for cervical dysplasia (i.e. ascertaining whether or not the marker is present) in the patient in the absence of any cytological examination.

Abstract: A method for inducing immunological tolerance in mammals which comprises feeding an antigen to a mammal, wherein the mammal is not allowed to ingest a fat-soluble component or a fat-soluble component-containing substance simultaneous with ingestion of the antigen, and an immunological tolerance inducing food kit and an immunological tolerance inducer kit which comprise an antigen-containing preparation containing no fat-soluble component and an antigen-free preparation containing no fat-soluble component. According to this invention, immunological tolerance can be induced effectively.

Abstract: An improved immunomodulatory therapy for enhancement of depressed host defense mechanisms and improving allograft survival rates comprising the use of omega-9 unsaturated fatty acids to alter the immune response associated with organ transplantation. It is administered optionally in conjunction with an immunomodulatory diet comprising arginine and its salts, or metabolic precursors of arginine, together with an immuno-suppressive treatment comprising the administration of cyclosporine or other immuno-suppressants and optionally, with or without a donor specific transfusion. An especially preferred source of the omega-9 unsaturated fatty acids is canola oil.

Abstract: This invention comprises cellular vaccines and methods of using them in cancer immunotherapy, particularly in humans. The vaccines comprise stimulated lymphocytes allogeneic to the subject being treated, along with a source of tumor-associated antigen. The allogeneic lymphocytes can be stimulated by combining or coculturing them with leukocytes obtained from the subject to be treated or from another third-party donor. Tumor antigen may be provided in the form of primary tumor cells, tumor cell lines or tumor extracts prepared from the subject. Stimulated allogeneic lymphocytes and tumor antigen are combined and administered at a site distant from the primary tumor, in order to prime or boost a systemic cellular anti-tumor immune response. This approach overcomes the natural refractory nature of the immune system to stimulation by tumor antigens, generating a host response and potentially improving the clinical outcome.

Abstract: Testing methods are provided for determining whether given candidate compounds are effective for regulating NF-&kgr;B, JNK and apoptosis cell activities. The methods involve forming a mixture including a compound such as a proteinaceous specie containing two death effector domains (DEDs) or structural or functional homologs and analogs thereof, the candidate compound and a binding target capable of specifically binding to at least one of the DEDs. This mixture is incubated under conditions such that, but for the presence of the candidate compound, the cell activity takes place to a determinable extent. After incubation, the activity is determined and is compared with the determinable extent thereof in the absence of the candidate compound. The assays may be carried out intracellularly or in a cell-free assay.

Abstract: The present invention features a method of producing a multimeric protein from a hybrid cell formed from the fusion of two or more cells, each of which cell is engineered to express one component of the multimeric protein, as well as a method for screening for successful fusion of the cells to produce a desired hybrid cell. The methods of the invention are widely applicable to the production of proteins having two or more components.

Abstract: The present invention relates to monoclonal antibody H11 and antigen binding fragments that specifically bind to the antigen recognized by H11, the C-antigen. The C-antigen is found specifically on neoplastic cells and not on normal cells. Also disclosed are polynucleotide and polypeptide derivatives based on H11, including single chain V region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the H11 antibody is effective in diagnosing, localizing, and/or treating neoplasias. The invention further provides methods for treating a neoplastic disease, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell lung carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Patients may also be treated concurrently with the antibodies and traditional anti-neoplastic agents.

Abstract: This invention provides a method for determining whether a compound is capable of suppressing ras functions comprising: (a) contacting an effective amount of the compound with Ha-ras transformed cloned rat embryo fibroblast cells under conditions permitting the compound to suppress ras functions in the cells; and (b) determining the expression or inhibition of certain indicator gene or genes, thereby determining whether the compound is capable of suppressing ras function. This invention further provides the determined compound and a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier. This invention also provides methods for generating transcriptional switched Ha-ras transformed cloned rat embryo fibroblast cells. This invention also provides the generated cells and different uses of the cells.

Abstract: This invention provides methods and compositions for treating tumors by implanting near the tumor an alloactivated cell population. The cell population is made up of a plurality of third-party donor cells that have been cultured together ex vivo, and harvested near the time of peak cytokine secretion. Once placed in the tumor bed, the alloactivated cells recruit active participation of the host, which then reacts against the tumor and provides a level of ongoing protection. Employing multiple third party donor cells confers particular advantages in terms of effectiveness, timing, and ease of use.

Abstract: A method of imaging apoptosis in vivo, using radiolabeled annexin, is described.

Abstract: Therapeutic multispecific compounds comprised of anti-Fc&agr; receptor antibodies and methods of use are provided.

Abstract: The present invention is directed to compositions and methods for selective induction of apoptosis in cancer cells, particularly malignant cancer cells, by delivery of a IL-1&agr; propiece polypeptide (e.g., a native IL-1&agr; propiece polypeptide, including IL-1&agr; propiece polypeptide variant) to a cancer cell.

Abstract: The present invention relates to improved semi-allogeneic immunogenic cells which act to stimulate and induce an immunological response when administered to an individual. In particular, it relates to cells which express both allogeneic and syngeneic MHC determinants and which also express at least one antigen recognized by T lymphocytes. The invention is also directed to methods of inducing an immune response and methods of treating tumors by administering the semi-allogeneic immunogenic cells to an individual.