Abstract: The present invention features a method of inducing donor-specific tolerance in a host. Tolerogenic treatments of the present invention may be administered to a host prior to transplantation of donor-derived materials. The tolerogenic treatment involves (1) administering an immunosuppressive agent to a host mammal in a non-myeloablative regimen sufficient to decrease, but not necessarily to eliminate, the host mammal's functional T lymphocyte population; (2) infusing donor antigens from a non-syngeneic donor into the host mammal; (3) eliminating those host T lymphocytes responding to the infused donor antigens using a non-myeloablative dose of lymphocytotoxic or tolerizing agent; and (4) administering donor hematopoietic cells to the host mammal. Donor lymphoid cells used for cell therapy of a host mammal can be depleted of host specific immunological reactivity by methods essentially similar to those use for tolerizing a host mammal prior to transplantation.

Abstract: A cellular immunogen is provided for immunizing a host against the effects of the product of a target proto-oncogene, where the overexpression of the target proto-oncogene is associated with a malignancy. The cellular immunogen comprises host cells which have been transfected with at least one transgene construct comprising a transgene cognate to the target proto-oncogene and a strong promoter to drive the expression of the transgene in the transfected cells. The transgene encodes a gene product which induces host immunoreactivity to host self-determinants of the product of the target proto-oncogene gene. The transgene may comprise, for example, wild-type or mutant retroviral oncogene DNA cognate to the target proto-oncogene; or wild-type or mutant proto-oncogene DNA of a species different from the host species. The cellular immunogen may be prepared from biopsied host cells, e.g. skin fibroblasts, which are stably or transiently transfected with the transgene construct containing the cognate transgene.

Abstract: The present invention relates to methods of treatment of programmed cell death (apoptosis) through the use of the HSV-1 gene &ggr;134.5 or the product of its expression, ICP34.5. The gene and its expression have been demonstrated to be required for HSV-1 neurovirulence, and in particular, to act as an inhibitor of neuronal programmed cell death which allows for viral replication. Use of the gene therapy, or the protein itself, can be expected to result in inhibition of programmed cell death in various neurodegenerative diseases. This invention also relates to novel vectors for gene therapy, including modified herpes virus. Methods are presented for conducting assays for substances capable of mimicing, potentiating or inhibiting the expression of &ggr;134.5 or the activity of ICP34.5. Also, methods are disclosed for the treatment of tumorogenic diseases, including cancer, and for treatment of herpes and other viral infections using inhibitors of &ggr;134.5 expression or ICP34.5 activity.

Abstract: A molecular complex comprising a gene encoding interferon releasably linked to a conjugate of a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. In a preferred embodiment, the gene encodes human IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The complex can be used to obtain targeted expression of interferon in selected cells either in vivo or in vitro.

Abstract: The present invention relates to a newly identified human ubiquitin protease belonging to the family of mammalian deubiquitinating enzymes. The invention also relates to polynucleotides encoding the ubiquitin protease. The invention further relates to methods using the ubiquitin protease polypeptides and polynucleotides as a target for diagnosis and treatment in ubiquitin-mediated or -related disorders. The invention further relates to drug-screening methods using the ubiquitin protease polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the ubiquitin protease polypeptides and polynucleotides. The invention further relates to procedures for producing the ubiquitin protease polypeptides and polynucleotides.

Abstract: The present invention relates to a composition and method useful for treating cancer in the urinary bladder. The present invention particularly relates to a composition comprising a Mycobacterium phlei deoxyribonucleic acid (M-DNA)-Mycobacterium phlei cell wall complex (MCC), wherein the M-DNA is preserved and complexed on the Mycobacterium phlei cell wall, and a pharmaceutically acceptable carrier. The MCC composition inhibits proliferation of and induces apoptosis in cancer cells in the urinary bladder and stimulates the responsive cells of the immune system to produce cytokines and reactive oxygen species. Methods of making MCC and methods of using MCC also are disclosed.

Abstract: The present invention relates to a composition and method useful for stimulating the immune system and for inhibiting proliferation of and inducing apoptosis in responsive cells of an animal. The present invention further relates to a composition comprising a Mycobacterium phlei deoxyribonucleic acid (M-DNA)-Mycobacterium phlei cell wall complex (MCC), wherein the Mycobacterium phlei-DNA is preserved and complexed on the Mycobacterium phlei cell wall, and a pharmaceutically acceptable carrier. MCC stimulates responsive cells of the immune system to produce cytokines and reactive oxygen species and inhibits proliferation of and induces apoptosis in responsive cells, including cancer cells, in an animal. Methods of making MCC and methods of using MCC also are disclosed.

Abstract: Immunocompromised or immunosuppressed non-primate chimeric mammalian hosts comprising a neuronal graft in the eye are provided for studying various events associated with humans. Particularly, the chimeric host may have solely human fetal neuronal xenografts or other fetal xenografts with other tissue, where the various tissues may be studied as to their response to a variety of agents, their response to pathogens or other diseased states, or their response to agents for the treatment of the various indications.

Abstract: The invention relates generally to compositions of and methods for obtaining and using a polypeptide other than BCL-2 that affects programmed vertebrate cell death. The invention relates as well to polynucleotides encoding those polypeptides, recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant polypeptides. The invention further provides methods for using the isolated, recombinant polypeptides in assays designed to select and improve substances capable of altering programmed cell death for use in diagnostic, drug design and therapeutic applications.

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: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided.

Abstract: A method for the direct in vivo transformation of cells in and surrounding a solid tumor is disclosed. This method is based on the site-specific delivery of proteins to solid tumors and to tissue surrounding the solid tumor by direct injection of a nucleic acid sequence. In particular, this method is directed to site-specific delivery of nucleic acids encoding major histocompatibility proteins, cytokines, and toxins to a solid tumor. This technique provides for the transfer of vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of disease.

Abstract: The present invention is directed to an isoform of the p53 tumor suppressor and to polynucleotides that encode this isoform. The isoform may be used as a marker to indicate that cardiac cells have experienced hypoxia, as would occur during a myocardial infarction. In addition, vectors encoding the isoform may be transfected into cells as a means of regulating proliferation.

Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: A novel growth factor, artemin, which belongs to the GDNF/neurturin/persephin family of growth factors, is disclosed. The human and mouse amino sequences have been identified. Human and mouse artemin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using artemin, methods for detecting artemin gene alterations and methods for detecting and monitoring patient levels of artemin are provided.

Abstract: The toxicity problems which occur when foreign material is introduced into higher eukaryotic cells, particularly during transfection with DNA, are countered by causing gene products to be expressed in the cell, which block the apoptosis triggered by the transfection process, and/or by treating the cells with anti-inflammatory substances. Preferably, Bcl-2, E1B 19K or an anti-apoptotically active gene of chicken adenovirus CELO is used as the anti-apoptosis gene whilst the inflammatory substance used is adenovirus VA1, which is introduced into the cell in the form of VA1-DNA. Using these methods, long-lasting gene expression can be achieved.

Abstract: A gene delivery vector used to generate genetically modified dendritic cells and B-cells central to the immune system. As a result, genetic modification of cells bearing the CD40 target antigen on its surface can be used to modulate immunity. Previously, both dendritic cells and B-cells have been resistant to gene transfer. The present invention serves to mediate dramatic enhancements in gene transfer to these cell types. Simultaneous with gene transfer, the vector system described herein matures dendritic cells and B-cells to a more potent immunoregulatory status. This invention provides technology for genetic manipulation of dendritic cells and B-cells.

Abstract: A neurogenesis inducing gene coding for the following protein (a) or (b): (a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2 (b) a protein which consists of the amino acid sequence shown in SEQ ID NO: 2 having deletion, substitution or addition of at least one amino acid and which has neurogenesis inducing activity.

Abstract: The present invention relates to the application of genetic engineering to provide a treatment of autoimmune disease. This is achieved preferably through the introduction of one or more recombinant genes encoding self antigens which are the target of an autoimmune response. In particular the invention provides a method of designing and constructing a gene encoding an encephalogenic epitope of proteolipid protein, and to the in vivo expression of the gene product by a recombinant retroviral vector. The expression and secretion of the encephalogenic epitope ameliorates the histopathological and clinical characteristics of experimental autoimmune encephalomyelitis (EAE) in the mouse model for multiple sclerosis (MS).

Abstract: Isolated nucleic acid molecules encoding human c-Maf, and isolated c-Maf proteins, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a human c-Maf transgene. The invention further provides human c-Maf fusion proteins and anti-human c-Maf antibodies. Methods of using the human c-maf compositions of the invention are also disclosed, including methods for detecting human c-Maf activity in a biological sample, methods of modulating human c-Maf activity in a cell, and methods for identifying agents that modulate the activity of human c-Maf.