Abstract: Disclosed is a mesenchymal stem cell and/or cell of the adipocyte lineage that (i) has been modified to have at least one exogenous antigen bound to at least one primary surface molecule of said cell such that said at least one antigen can initiate an immune response and (ii) also expresses at least one co-stimulatory molecule. The antigen is preferably a protein, polypeptide, lipid or glycolipid. The primary surface molecule is MHC I, MHC II or CD1. Also disclosed is a method for stimulating presentation of at least one exogenous antigen fragment on a mesenchymal stem cell primary surface molecule by contacting a mesenchymal stem cell that is capable of expressing at least one co-stimulatory molecule with (i) an exogenous antigen or (ii) genetic material that codes for the exogenous antigen which the mesenchymal stem cell processes into at least one antigen fragment. The method can further include contacting the mesenchymal stem cell with interferon-?.

Abstract: Transgenic non-human mammals comprising a DNA with an exogenous IL-18 gene incorporated in it such that the exogenous IL-18 gene is skin-specifically expressed, or their offsprings. The transgenic non-human mammals according to the present invention spontaneously develop atopic dermatitis under specific pathogen-free conditions, and therefore, are useful as disease model animals. Use of the transgenic non-human mammals according to the present invention makes it possible to develop drugs for preventing or treating atopic dermatitis by natural immunity and also to elucidate the onset mechanisms of atopic diseases.

Abstract: The invention provides methods and materials related to animals having a disrupted IEX-1 sequence. For example, the invention provides homozygous knockout (IEX-1?/?) animals and heterozygous (IEX-1?/+) animals.

Abstract: The present invention provides delivery systems for and methods of delivering conduction protein genetic material to cardiac cells in localized areas of the heart to improve the conductance therein. More specifically, there is provided a system and method for delivering connexin proteins or nucleic acid molecules encoding connexin proteins to a site in the heart which has been determined by mapping procedures to have a conduction disturbance. For cases where conduction is impaired, selected genetic material is delivered to cells around the disturbance area, in order to enhance overall conductivity patterns; in other cases, genetic material is selected to slow conduction in affected areas, so as to prevent, e.g., brady-tachy syndrome.

Abstract: The present invention provides methods and compositions for conferring tumor selective cell death on cancer cells expressing specific target precursor messenger RNA molecules (cancer cell selective target pre-mRNAs). The compositions of the invention include conditionally replicative adenoviruses that have been genetically engineered to express one or more pre-trans-splicing molecules (PTMs) designed to interact with one or more cancer cell target pre-mRNA and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecules (chimeric RNA) capable of encoding adenovirus specific protein(s). Adenovirus specific proteins include those proteins complementing an essential activity necessary for replication of a defective adenovirus. The methods and compositions of the invention may be used to target a lytic adenovirus infection to cancer cells thereby providing a method for selective destruction of cancer cells.

Abstract: An animal suitable as a model for an allergic disorder, wherein the animal is an immuno-modulated animal which has been sensitized with an antigen under a specific pathogen free environment such that when the animal displays allergy symptoms caused by the antigen.

Abstract: A new gene therapy entails tumor treatment by introducing an expressible nucleotide sequence for a soluble costimulatory factor, thereby enhancing the response of T-cells to a tumor. In vivo expression of the soluble factor overcomes anergy or tolerance to tumor cells and activates T-cells that are infiltrating or surrounding the tumor. A pharmaceutical composition containing such a gene is effective in tumor suppression.

Abstract: The present invention relates to transgenic non-human animals that are engineered to contain human immunoglobulin gene loci. In particular, animals in accordance with the invention possess human Ig loci that include plural variable (VH and V?) gene regions. Advantageously, the inclusion of plural variable region genes enhances the specificity and diversity of human antibodies produced by the animal. Further, the inclusion of such regions enhances and reconstitutes B-cell development to the animals, such that the animals possess abundant mature B-cells secreting extremely high affinity antibodies.

Abstract: The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (?-AR). ?-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a ?-AR transgene, a ?-ARK transgene, or a ?-ARK inhibitor transgene.

Abstract: The present invention relates to devices, systems and methods for treating tumors. In particular, the present invention relates to enclosures housing cell-coated supports for promoting regression of tumors, such as cancerous tumors, papillomas, and warts. In preferred embodiments, the present invention provides methods of promoting tumor regression employing enclosures secreting therapeutic proteins.

Abstract: The present invention provides fully human antibodies in a transgenic animal of a desired isotype in response to immunization with any virtually any desired antigen. The human immunoglobulin heavy chain transgene in the foregoing animals comprises a human constant region gene segment comprising exons encoding the desired heavy chain isotype, operably linked to switch segments from a constant region of a different heavy chain isotype, i.e., a non-cognate switch region. Said additional constant region segment comprises a switch region and human constant region coding segment, wherein the constant region coding segment is operably linked to a switch region that it is not normally associated with, i.e., a non-cognate switch region. In the transgenes of the invention, the non-cognate switch region may be a switch region from a different species than the constant region coding segment.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: An immunotherapeutic vaccine providing antigen presenting cells that have been pulsed with a disrupted cell preparation which includes enucleated cytosol and cell membranes of cancer cells infected with a recombinant vaccinia virus encoding at least one immunostimulating molecule. In a preferred embodiment, the vaccine includes autologous dendritic/monocytic cells (DC/M) that present a mixture of antigens (present in the enucleated cytosol and cell membranes) from melanoma cell lines that have been infected with a recombinant vaccinia virus encoding IL-2. In another of the preferred embodiments, the enucleated cytosol and cell membranes are from melanoma cells harvested from the patient to be treated. A method of making the vaccine and methods of using the vaccine to stimulate an anti-cancer immune response and to treat a patient with a cancer are also described.

Abstract: An improved method for the production of monoclonal antibodies is disclosed.

Abstract: A method for treating tumors. Through infusion or xenotransplantation of xenogeneic cells, such as infusion of murine cells into the peritoneal cavity of humans, a hyperacute rejection response to the cells is induced. This in turn creates a bystander effect to the tumor. This effect creates tumor regression. This treatment can be used alone or in conjunction with gene therapy or chemotherapy treatments.

Abstract: A method of providing a therapeutic effect in a human patient which comprises administering to the patient CD34+ cells obtained from cord blood. The CD34+ cells have been engineered with at least one nucleic acid sequence encoding a therapeutic agent. Such CD34+ cells may be engineered by transducing the cells with a retroviral vector including the nucleic acid sequence encoding the therapeutic agent. This method has been applied in treating newborn infants suffering from ADA deficiency.

Abstract: This invention is directed to a modified cyclosporin A and to a modified, genetically engineered version of its receptor, cyclophilin. This invention is further directed to a method for treating host versus graft disease following blood marrow transplantation by transfecting stem cells so that after introduction into a patient the stem cells will express the modified cyclophilin, and, as necessary, administer the modified cyclosporin A to the patient.

Abstract: The invention provides isolated dendritic cells genetically modified to express a selectin polypeptide, optionally treated with activated platelets or membrane microparticles thereof. The invention also provides isolated platelet modified dendritic cells. Methods for delivering the modified dendritic cells to peripheral lymph nodes and methods for using the modified dendritic cells to stimulate immune responses also are provided. Vaccine compositions containing the modified dendritic cells also are provided.

Abstract: The present invention relates to compositions and methods relating to MEK5 and its role in heart disease. This protein has now been identified as a target for therapeutic intervention due to its role molecular events that lead to or contribute to cardiac hypertrophy and/or dilated cardiomyopathy. In particular, inhibition of MEK5 activity will lead to decrease signalling of the pathways and reduce or eliminate the effects on sarcomere assembly, which in turn result or contribute to cardiac dysfunction. Also provided are transgenic animals and methods of screening for inhibitors of MEK5.

Abstract: Genetically engineered cells are provided which can serve as universal donor cells in such applications as reconstruction of vascular linings or the administration of therapeutic agents. The cells include a coding region which provides protection against complement-based lysis, i.e., hyperacute rejection. In addition, the cell's natural genome is changed so that functional proteins encoded by either the class II or both the class I and the class II major histocompatibility complex genes do not appear on the cell's surface. In this way, attack by T-cells is avoided. Optionally, the cells can include a self-destruction mechanism so that they can be removed from the host when no longer needed.