Abstract: An objective of the present invention is to provide vectors for conveniently and efficiently producing ES-like cells in which foreign genes are not integrated into the chromosome. The present inventors discovered methods for producing ES-like cells from somatic cells using chromosomally non-integrating viral vectors. Since no foreign gene is integrated into the chromosome of the produced ES-like cells, they are advantageous in tests and research, and immunological rejection and ethical problems can be avoided in disease treatments.

Abstract: The present invention provides anticancer agents comprising dendritic cells introduced with RNA viruses. The present invention also provides methods for producing anticancer agents, which comprise the step of preparing dendritic cells introduced with RNA viruses. The present invention also provides methods for treating cancers using dendritic cells introduced with RNA viruses. The present invention provides effective methods for treating cancers, which use RNA viruses and dendritic cells in combination.

Abstract: An objective of the present invention is to provide methods for producing dendritic cells (DCs), which comprise the step of culturing DC precursor cells in the presence of a plurality of cytokines, produced dendritic cells, and uses thereof. The present inventors discovered that dendritic cells with a high IL-12 productivity can be obtained by culturing DC precursor cells in the presence of a plurality of cytokines, followed by about one week of culture in the presence of GM-CSF and IL-4. The present invention enables preparation of a large amount of DCs with a high IL-12 productivity from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immune therapy, treatment of infections, etc. Thus, the effect of DC vaccines is expected to be enhanced.

Abstract: A technique is needed which can amplify NK cells in vitro and prepare optimum number of NK cells for the adoptive immunotherapy. A method for amplifying NK cells is provided which comprises steps of: preparing cell population which is comprised of NK cells, removing T cells from the cell population which is comprised of NK cells, and, after removal of T cells, cultivating the remaining cells in a medium supplemented with 2500 to 2831 IU/mL of IL-2. The method for amplifying NK cells of the present invention may comprise a step of removing hematopoietic progenitor cells from the cell population. The present invention provides a pharmaceutical composition for adoptive immunotherapy, comprising NK cells which are prepared by the amplifying method of the present invention.

Abstract: The present invention provides methods for producing DCs, which comprise the step of culturing DC precursor cells in the presence of multiple cytokines, dendritic cells produced thereby, and uses thereof. The methods of the present invention enable production of large quantities of DC precursors with a high ability to differentiate into DCs. The present invention enables one to obtain large quantities of DCs from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immunotherapy, treatment of infection, and such. Thus, an enhancement is expected for the effect of DC vaccines.

Abstract: The present invention provides novel methods for treating diseases associated with apoptotic degeneration in ocular tissue cells by effective administration of pigment epithelium derived factor (PEDF). The present inventors studied PEDF as a means to prevent ganglion cell death, the final pathology of glaucoma. The present invention is particularly focused on SIV vectors for effective methods for delivering PEDF, and constructed an SIV-PEDF vector. When the SIV-PEDF vector was administered subretinally to an ischemia reperfusion model and NMDA-induced model, a significant suppression effect on ganglion cell death was observed. The present inventors therefore discovered that the SIV-PEDF vector is an effective pharmaceutical agent for treating diseases associated with apoptotic degeneration in ocular tissue cells, such as glaucoma.

Abstract: The present invention provides Paramyxovirus vectors encoding angiogenic genes and use of the same. The use of Paramyxovirus vectors enables effective transfer of angiogenic genes into individual tissues. FGF2 gene transferred into ischemic tissues in vivo induces expression of angiogenic genes without causing edema, and prevents necrosis due to ischemia. The vectors of the present invention are suitable for gene therapy targeted to ischemic tissues.

Abstract: An objective of the present invention is to provide methods for producing dendritic cells (DCs), which comprise the step of culturing DC precursor cells in the presence of a plurality of cytokines, produced dendritic cells, and uses thereof. The present inventors discovered that dendritic cells with a high IL-12 productivity can be obtained by culturing DC precursor cells in the presence of a plurality of cytokines, followed by about one week of culture in the presence of GM-CSF and IL-4. The present invention enables preparation of a large amount of DCs with a high IL-12 productivity from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immune therapy, treatment of infections, etc. Thus, the effect of DC vaccines is expected to be enhanced.

Abstract: An objective of the present invention is to provide vectors for conveniently and efficiently producing ES-like cells in which foreign genes are not integrated into the chromosome. The present inventors discovered methods for producing ES-like cells from somatic cells using chromosomally non-integrating viral vectors. Since no foreign gene is integrated into the chromosome of the produced ES-like cells, they are advantageous in tests and research, and immunological rejection and ethical problems can be avoided in disease treatments.

Abstract: The present invention provides Paramyxovirus vectors encoding angiogenic genes and use of the same. The use of Paramyxovirus vectors enables effective transfer of angiogenic genes into individual tissues. FGF2 gene transferred into ischemic tissues in vivo induces expression of angiogenic genes without causing edema, and prevents necrosis due to ischemia. The vectors of the present invention are suitable for gene therapy targeted to ischemic tissues.

Abstract: The present invention provides methods for producing DCs, which comprise the step of culturing DC precursor cells in the presence of multiple cytokines, dendritic cells produced thereby, and uses thereof. The methods of the present invention enable production of large quantities of DC precursors with a high ability to differentiate into DCs. The present invention enables one to obtain large quantities of DCs from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immunotherapy, treatment of infection, and such. Thus, an enhancement is expected for the effect of DC vaccines.

Abstract: The present invention provides Paramyxovirus vectors encoding angiogenic genes and use of the same. The use of Paramyxovirus vectors enables effective transfer of angiogenic genes into individual tissues. FGF2 gene transferred into ischemic tissues in vivo induces expression of angiogenic genes without causing edema, and prevents necrosis due to ischemia. The vectors of the present invention are suitable for gene therapy targeted to ischemic tissues.

Abstract: The present invention provides novel methods for treating diseases associated with apoptotic degeneration in ocular tissue cells by effective administration of pigment epithelium derived factor (PEDF). The present inventors studied PEDF as a means to prevent ganglion cell death, the final pathology of glaucoma. The present invention is particularly focused on SIV vectors for effective methods for delivering PEDF, and constructed an SIV-PEDF vector. When the SIV-PEDF vector was administered subretinally to an ischemia reperfusion model and NMDA-induced model, a significant suppression effect on ganglion cell death was observed. The present inventors therefore discovered that the SIV-PEDF vector is an effective pharmaceutical agent for treating diseases associated with apoptotic degeneration in ocular tissue cells, such as glaucoma.

Abstract: An objective of the present invention is to provide a safe and effective vaccine therapy for Alzheimer's disease. A minus strand RNA viral vector carrying amyloid gene was constructed, and administered intranasally to 24- to 25-months-old APP transgenic mice. The level of serum anti-A 42 antibody was determined and showed to be markedly higher than the control. The results of histological investigation showed that the administration of a vector of the present invention markedly reduced senile plaques in all of the frontal lobe, parietal lobe, and hippocampus. The brain A level was also markedly reduced. Furthermore, the administration of a vector of the present invention did not result in lymphocyte infiltration in the central nervous system.

Abstract: The present invention provides a retroviral vector containing a membrane protein having a hemagglutinin activity. The present inventors constructed a retroviral vector pseudotyped by the membrane protein having a hemagglutinin activity. This viral vector showed gene transfer at a high efficiency into host cells. In particular, it was established that genes can be transferred thereby at a high efficiency into cells into which genes can hardly be transferred by the conventional techniques, for example, blood cells and hematopoietic cells including hematopoietic stem cells, and mucous cells including mucosa epithelial cells. The viral vector of the present invention is highly useful as a vector for gene therapy.

Abstract: The present invention provides methods for suppressing tumor proliferation comprising the step of inhibiting the expression of PDGF-A or the binding between PDGF-A homodimers and PDGFR?. Activation of the PDGFR?-p70S6K signal transduction pathway by PDGF-AA is an important factor in tumor angiogenesis and relates to the prognosis of patients suffering from tumors. By inhibiting PDGF-A expression in tumors or in their surrounding tissues, or by inhibiting the binding between PDGF-A homodimers and PDGFR?, the formation and retention of tumor vasculature can be inhibited, thereby suppressing tumor proliferation.

Abstract: Minus-strand RNA viruses were found to have an effective tumor-suppressive effect even when they did not carry a therapeutically effective gene. The present invention provides anticancer agents comprising a minus-strand RNA virus. Furthermore, the present invention provides methods for producing the anticancer agents, which comprise the step of mixing a minus-strand RNA virus with pharmaceutically acceptable carriers. Furthermore, the present invention provides methods for suppressing cancer, which comprise the step of administering a minus-strand RNA virus to cancer tissues.

Abstract: The present invention provides anticancer agents comprising dendritic cells introduced with RNA viruses. The present invention also provides methods for producing anticancer agents, which comprise the step of preparing dendritic cells introduced with RNA viruses. The present invention also provides methods for treating cancers using dendritic cells introduced with RNA viruses.

Abstract: Provided are a recombinant Sendai virus vector for introducing exogenous genes to airway epithelia and a method for introducing exogenous genes using the vector. The recombinant Sendai virus vector enables efficient gene transfer to native mucus-layered airway epithelial cells by briefly contacting the vector with the cells. Furthermore, the vector can introduce genes to not only apical surfaces but also submucosal glands where CFTR primarily expresses. The vector can thus be used for gene therapy of CF, a CFTR-deficient disease.

Abstract: The present invention provides a prophylactic and/or therapeutic agent for pulmonary hypertension, comprising an antagonistic mutein of MCP-1 or a salt thereof, a DNA molecule comprising a nucleotide sequence encoding the antagonistic mutein of MCP-1, or a neutralizing antibody against MCP-1. The antagonistic mutein of MCP-1 or a salt thereof, the DNA molecule having a nucleotide sequence encoding the antagonistic mutein of MCP-1, or the neutralizing antibody against MCP-1 has hypotensive activity, and thus is useful as a pharmaceutical agent for preventing and/or treating pulmonary hypertension (primary pulmonary hypertension, in particular).