Abstract: Exogenous cDNA capable of expressing interferon ? activity, exogenous interferon ? protein, inducers of endogenous interferon ? protein activity, inducers of endogenous interferon ? protein activity, inducers of endogenous interfereon ? activity, or inducers of other immune-enhancing activity can be combined with a vaccine to enhance an immune response. Specifically disclosed are adjuvant and vaccine combinations where the adjuvant comprises a cDNA capable of expressing interferon ? activity, a complex comprising polyriboinosinic-polyribocytidilic acid, or a complex comprising polyriboinosinic-polyribocytidilic acid, poly-L-lysine, and carboxymethylcellulose and where the vaccine is a live vaccine virus derived from a virus causing porcine reproductive and respiratory syndrome disease.

Abstract: A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells and/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation.

Abstract: The invention provides a transgenic animal carrying two transgenes, one encoding a human decay accelerating factor (hDAF) and the other encoding a human heme oxygenase-1 (hHO)-1, which are useful for providing cells, tissues or organs therefrom for xenotransplantation.

Abstract: The present invention relates to a method for inducing the immune response of an individual against B-lymphoproliferative disorders. The method is based on DNA vaccination with the short peptide encompassing the CDR3 hypervariable region of immunoglobulin heavy chain (VH-CDR3) alone or in combination with at least another immunomodulating sequence.

Abstract: The present invention provides a Fc?RIIa transgenic non-human animal model for autoimmune disease, particularly arthritis. This invention also provides a method of using this model to screen compounds that can reduce aberrant immune activity including aberrant immune complex formation aberrant immune complex clearance and immune complex induced inflammation. This invention also provides means of using this model to treat or prevent autoimmune disease.

Abstract: The present invention provides a neurodegenerative, non-human transgenic mammal whose cells contain a TrkA-hFc transgene for encoding at least a TrkA fusion protein and the use thereof.

Abstract: A transgenic mouse is disclosed herein whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor. A mouse homozygous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function. A method is disclosed for altering a B cell activity. The method includes administering a therapeutically effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity. A method is also disclosed for of treating a subject with Job's disorder or atopic disease. A method is also disclosed for treating or preventing an allergic reaction in a subject. A method is also disclosed for treating a subject with an autoimmune or antibody mediated disorder.

Abstract: The present invention provides methods for enhancing host immunity to a virus and/or a cancer and methods for enhancing the cytotoxic T-cell (CTL) mediated immune responses by providing granzyme B inhibitors to a subject. One objective of the invention is to induce long-term protective immunity to a subject in need thereof This is accomplished by providing granzyme inhibitors to the subject which increase the number of memory-CTLs and thereby prevent or alleviate viral infections and/or treat. Providing granzyme inhibitors is also effective in the prevention of cancers. Some examples of granzyme inhibitors contemplated within the present invention include the endogenous serpins such as SPI6 and PI9, other suicide substrates of granzyme B, granzyme B antibodies, etc. Also provided are methods for expression of nucleic acids encoding granzyme inhibitors in cytotoxic T-lymphocytes (CTLs).

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: Cells transformed to express on their surface a component which binds to an Fc receptor of an effector cell are disclosed. Also disclosed are expression vectors used to transform the cells. Once transformed, the cells bind to effector cells via the Fc receptor of the effector cell to stimulate an effector cell mediated immune response.

Abstract: An object of the present invention is to provide a nonhuman model animal of Th2-mediated hyperimmune response lacking PIR-B gene function on its chromosome by which the Th2-mediated immune response mechanism and allergy onset mechanism in vivo can be analyzed and which is liable to suffer from not only hyper-response of B cells but also allergy, and an inducer/promoter or an inhibitor for Th2-mediated immune response, etc. with the use of the nonhuman model animal of Th2-mediated hyperimmune response. The nonhuman model animal of Th2-mediated hyperimmune response is prepared by integrating a fragment comprising exons 1 to 7 and the domain in the 5? side of exon 8 of mouse PIR-B gene and another fragment containing exons 10 to 14 into a vector pMC1-Neo, cleaving it with Xho I-Sal I, integrating it into a vector pIC19R-MC1tk having herpes virus thymidine kinase to thereby construct targeting vector, transferring the targeting vector into ES cells and then injecting the ES cells into blastcyst.

Abstract: The present invention relates to novel vaccines against malaria infections, based on recombinant viral vectors, such as alpha viruses, adenoviruses or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Novel codon-optimized circumsporozoite genes are disclosed. Preferably, replication-defective adenoviruses are used, derived from serotypes that encounter low titers of neutralizing antibodies. The invention, therefore, also relates to the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.

Abstract: The present invention provides methods of delaying development of CEA-associated tumors using the anti-idiotype antibody 3H1, particularly in high-risk individuals.

Abstract: Restenosis in a subject can be treated by administering to a tissue, e.g., a blood vessel, of the subject an agent that increases SERCA activity. For example, a stent that is coated with the agent can be introduced into a blood vessel.

Abstract: The invention provides a method for stimulating an immune response by administering to a lymphoid tissue a nucleic acid molecule comprising an expression element operationally linked to a nucleic acid sequence encoding one or more heterologous epitopes. The heterologous epitope can be inserted into a complementarity-determining region of an immunoglobulin molecule. The invention also provides a nucleic acid molecule comprising a hematopoietic expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide. The invention additionally provides a method of treating a condition by administering a nucleic acid molecule comprising a hematopoietic cell expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide, wherein the nucleic acid molecule is targeted to a hematopoietic cell.

Abstract: The aim of the present invention is to provide a method of acquiring immunological tolerance to a foreign DNA or its expression product whereby the foreign DNA such as a vector carrying a foreign gene incorporated thereinto or its expression product can be recognized not as non-self but as self; a method of sustaining a gene therapeutic effect whereby a rejection to a foreign DNA such as a vector carrying a foreign gene incorporated thereinto or its expression product can be avoided; and a non-human animal which has acquired immunological tolerance to a foreign DNA such as a vector carrying a foreign gene incorporated thereinto or its expression product. Fetal immature T lymphocytes transferred with a foreign DNA, such as a foreign gene-incorporated viral vector, are introduced into thymus and said foreign DNA is expressed in the thymus organ.

Abstract: A method of transplanting a transplant derived from a donor into a recipient is disclosed. The method comprises the steps of (a) transplanting the transplant into the recipient; and (b) administering to the recipient a dose including non-alloreactive anti-third party cytotoxic T-lymphocytes (CTLs), wherein the non-alloreactive anti-third party CTLs are generated by directing T-lymphocytes of the donor against a third party antigen or antigens, the dose is substantially depleted of T-lymphocytes capable of developing into alloreactive CTLs, thereby preventing or ameliorating both graft rejection by the recipient and graft versus host disease.

Abstract: A method for enhancing the transfection efficiency of naked plasmid DNA in treating and/or preventing angiogenesis-dependent symptoms is provided by the present inventions. According to the present method, a suitable naked plasmid DNA is subjected for intramuscular injection under increased pressure inside the muscle or hyperbaric oxygen. Angiogenesis-dependent symptoms, including wounds, inflammatory diseases, critical limb ischemia, ischemia heart diseases, cerebral infarction, diabetic neuropathy, spinal canal stenosis, etc., may be treated by the present methods.

Abstract: Methods and pharmaceutical compositions for modifying cells of a mammalian recipient with DNA encoding a secreted protein such as human interferon in situ are provided. The methods include forming a secreted protein expression system in vivo or ex vivo and administering the expression system to the mammalian recipient. The expression system and methods are useful for the localized and systemic delivery of interferons in situ.

Abstract: Primary human cells which are genetically engineered with DNA (RNA) encoding a marker or therapeutic which is expressed to be expressed in vivo. Such engineered cells may be used in gene therapy.