Abstract: The present invention provides a DNA composition comprising a DNA minigene construct that encodes for a polypeptide comprising a plurality of immunogenic fragments of a cysteine endopeptidase that is expressed in tumor-associated cells. The immunogenic fragments are joined together serially by a linker peptide between each successive fragment in the polypeptide. The polypeptide is capable of eliciting an immune response against the tumor-associated cells, is expressible in immune cells, and is incorporated in a pharmaceutically acceptable carrier.

Abstract: A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a DNA construct operably encoding a cancer-associated Inhibitor of Apoptosis-family protein and an immunoactive gene product, such as a cytokine or a ligand for a natural killer cell surface receptor, in a pharmaceutically acceptable carrier. A preferred cytokine is CCL21. Preferred ligands for a natural killer cell surface receptor include human MICA, human MICB, human ULBP1, human ULBP2, and human ULBP3. The cancer-associated Inhibitor of Apoptosis (IAP)-family protein is preferably a survivin protein or livin protein. Method of inhibiting tumor growth by administering the vaccine of the invention to a mammal is also described.

Abstract: A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a DNA construct operably encoding a cancer-associated Inhibitor of Apoptosis-family protein and an immunoactive gene product, such as a cytokine or a ligand for a natural killer cell surface receptor, in a pharmaceutically acceptable carrier. A preferred cytokine is CCL21. Preferred ligands for a natural killer cell surface receptor include human MICA, human MICB, human ULBP1, human ULBP2, and human ULBP3. The cancer-associated Inhibitor of Apoptosis (IAP)-family protein is preferably a survivin protein or livin protein. Method of inhibiting tumor growth by administering the vaccine of the invention to a mammal is also described.

Abstract: The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalenetly attached to a legumain-binding moiety.

Abstract: A method of inhibiting endothelial cell proliferation in a mammal is provided. The method comprises the step of administering to the mammal an effective immunological response eliciting amount of a DNA composition comprising a DNA construct operably encoding a VEGF receptor polypeptide and a pharmaceutically acceptable carrier therefor, whereby said mammal exhibits an immune response elicited by vaccine and specific to proliferating endothelial cells. The methods of this invention inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalenetly attached to a legumain-binding moiety.

Abstract: A method of inhibiting endothelial cell proliferation in a mammal is provided. The method comprises the step of administering to the mammal an effective immunological response eliciting amount of a DNA composition comprising a DNA construct operably encoding a VEGF receptor polypeptide and a pharmaceutically acceptable carrier therefor, whereby said mammal exhibits an immune response elicited by vaccine and specific to proliferating endothelial cells. The methods of this invention inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: Disclosed are a method for producing a carbon nanotube (CNT) whereby, in the local synthesis of CNTs, a high resolution, a low cost, easiness in production and mass production capability can be established at the same time; and a two-dimensionally patterned CNT obtained thereby.

Abstract: A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA? dam? S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.

Abstract: A DNA composition effective for inhibiting endothelial cell proliferation comprises a DNA construct operably encoding a vascular endothelial growth factor (VEGF) receptor polypeptide, which can be a full length VEGF receptor protein or an immunogenic fragment thereof. This invention provides DNA compositions that encode VEGF receptor-2 (KDR), VEGF receptor-1 (Flt-1), or Flk-1 (the murine homolog of KDR), as well as methods of using such a DNA composition to inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA- dam- S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.

Abstract: The present invention provides a DNA composition comprising a DNA minigene construct that encodes for a polypeptide comprising a plurality of immunogenic fragments of a cysteine endopeptidase that is expressed in tumor-associated cells. The immunogenic fragments are joined together serially by a linker peptide between each successive fragment in the polypeptide. The polypeptide is capable of eliciting an immune response against the tumor-associated cells, is expressible in immune cells, and is incorporated in a pharmaceutically acceptable carrier.

Abstract: A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA? dam? S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.

Abstract: A DNA vaccine effective for eliciting an immune response against cells that present a carcinoembryonic antigen (CEA) comprises a DNA operably encoding a CEA and a DNA operably encoding a CD40 ligand, SEQ ID NO:1 and SEQ ID NO: 2, respectively, or its homotrimer, CD40LT. The DNA vaccine can be incorporated in a delivery vector such as an attenuated live bacterium or virus, or a liposome carrier. In a method embodiment, the DNA vaccine is administered orally to a mammal, such as a human, to elicit an immune response against CEA presenting cells such as colon cancer cells. A preferred method embodiment includes the additional step of treating the mammal with recombinant antibody fusion protein huKS1/4-IL2 to enhance the immune response effectiveness of the vaccine.

Abstract: A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA- dam- S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.

Abstract: A DNA composition effective for inhibiting endothelial cell proliferation comprises a DNA construct operably encoding a vascular endothelial growth factor (VEGF) receptor polypeptide, which can be a full length VEGF receptor protein or an immunogenic fragment thereof. This invention provides DNA compositions that encode VEGF receptor-2 (KDR), VEGF receptor-1 (Flt-1), or Flk-1 (the murine homolog of KDR), as well as methods of using such a DNA composition to inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: A DNA vaccine effective for inhibiting endothelial cell proliferation comprises a DNA construct operably encoding a vascular endothelial growth factor (VEGF) receptor protein. This invention provides DNA vaccines that encode VEGF receptor-2 (KDR, SEQ ID NO: 2), VEGF receptor-1 (Flt-1, (SEQ ID NO: 4), or Flk-1 (the murine homolog of KDR, SEQ ID NO: 6), DNA sequences SEQ ID NOS: 1, 3, and 5 respectively, as well as methods of using such a DNA vaccine to inhibit vascular endothelial cell proliferation in the tumor micro-environment. Anti-angiogenesis and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: Methods are disclosed for enhancing protein production. One method comprises preparing a vector by inserting a gene encoding ubiquitin in front of a gene encoding a protein of interest and inserting the vector into a cell. A fusion protein will be expressed which includes ubiquitin plus the protein of interest. Ubiquitin C-terminal hydrolases can cleave the fusion protein leaving the desired protein in its free state. This method causes enhanced production of the protein of interest as compared to performing the same method without the ubiquitin gene as part of the vector. A ubiquitin promoter is unnecessary to yield this enhanced production and is not used. A second method is very similar except that in place of a ubiquitin gene, a gene encoding fourteen amino acids of cucumber mosaic virus coat protein is inserted in front of the gene of interest. This results in expression of a fusion protein comprising the fourteen amino acid residues of the coat protein bonded to the protein of interest.

Abstract: A DNA vaccine effective for eliciting an immune response against cells that present a carcinoembryonic antigen (CEA) comprises a DNA operably encoding a CEA and a DNA operably encoding a CD40 ligand, SEQ ID NO:1 and SEQ ID NO: 2, respectively, or its homotrimer, CD40LT. The DNA vaccine can be incorporated in a delivery vector such as an attenuated live bacterium or virus, or a liposome carrier. In a method embodiment, the DNA vaccine is administered orally to a mammal, such as a human, to elicit an immune response against CEA presenting cells such as colon cancer cells. A preferred method embodiment includes the additional step of treating the mammal with recombinant antibody fusion protein huKS1/4-IL2 to enhance the immune response effectiveness of the vaccine.

Abstract: A DNA vaccine effective for eliciting an immune response against cells that present a carcinoembryonic antigen (CEA) comprises a DNA operably encoding a CEA and a DNA operably encoding a CD40 ligand, SEQ ID NO:1 and SEQ ID NO: 2, respectively, or its homotrimer, CD40LT. The DNA vaccine can be incorporated in a delivery vector such as an attenuated live bacterium or virus, or a liposome carrier. In a method embodiment, the DNA vaccine is administered orally to a mammal, such as a human, to elicit an immune response against CEA presenting cells such as colon cancer cells. A preferred method embodiment includes the additional step of treating the mammal with recombinant antibody fusion protein huKS1/4-IL2 to enhance the immune response effectiveness of the vaccine.