摘要:
The present invention provides a method for reducing the size of a tumor in a human comprising (a) directly injecting into the tumor, via multiple injections to different points of the tumor, a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) a replication-deficient adenoviral vector comprising a nucleic acid sequence encoding TNF-alpha operably linked to a promoter, wherein the dose comprises about 1x107 to about 4x1012 3 particle units (pu) of replication-deficient adenoviral vector, two or more times over a therapeutic period comprising up to 10 weeks, and (b) administering a dose of ionizing radiation over the duration of the therapeutic period, whereby the size of the tumor is reduced.
摘要:
The present invention provides a chimeric adenovirus coat protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence. Such a chimeric adenovirus coat protein according to the invention is able to direct entry into cells of a vector comprising the coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than the chimeric adenovirus coat protein. The chimeric coat protein preferably is a fiber, hexon, or penton protein. The present invention also provides an adenoviral vector that comprises the chimeric adenovirus coat protein, as well as methods of constructing and using such a vector.
摘要:
The invention provides a gene transfer vector and a conjugate comprising at least three contiguous amino acids of a shaft region of a subgroup C adenovirus fiber protein. The invention also provides methods of using the gene transfer vector and the conjugate to induce an immune response in a mammal, and to deliver a protein or a non-proteinaceous molecule to a specific cell type.
摘要:
A recombinant adenovirus comprising a chimeric penton base protein, wherein an RGD amino acid sequence is deleted from the penton base protein, a method of gene therapy involving the use of such adenovirus, and adenoviral transfer vectors for the generation of such recombinant adenovirus are provided.
摘要:
The present invention provides a chimeric adenovirus coat protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence. Such a chimeric adenovirus coat protein according to the invention is able to direct entry into cells of a vector comprising the coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than the chimeric adenovirus coat protein. The chimeric coat protein preferably is a fiber, hexon, or penton protein. The present invention also provides an adenoviral vector that comprises the chimeric adenovirus coat protein, as well as methods of constructing and using such a vector.
摘要:
The present invention provides a short-shafted adenoviral fiber, a recombinant adenovirus comprising a short-shafted fiber, a vector comprising a short-shafted adenoviral fiber gene, and a method of targeting attachment of a short-shafted recombinant adenovirus to a cell so as to effect entry of the short-shafted recombinant adenovirus into the cell.
摘要:
The present invention provides a method for reducing the size of a tumor in a human comprising (a) directly injecting into the tumor, via multiple injections to different points of the tumor, a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) a replication-deficient adenoviral vector comprising a nucleic acid sequence encoding TNF-alpha operably linked to a promoter, wherein the dose comprises about 1x107 to about 4x1012 3 particle units (pu) of replication-deficient adenoviral vector, two or more times over a therapeutic period comprising up to 10 weeks, and (b) administering a dose of ionizing radiation over the duration of the therapeutic period, whereby the size of the tumor is reduced.
摘要:
The present invention provides a method of producing an adenoviral vector stock by providing a culture of cells permissive for growth of adenoviral vectors, wherein the cells are in a medium, culturing the culture under conditions to permit growth of the cells, perfusing fresh medium trough the culture for a period of about 1-6 hours, in an amount of at least about two times the volume of medium in the culture, while the density of the cells in the medium is about 40-70 % of the density of cells obtained in the medium when the growth of the culture is in the stationary phase, contacting the culture with adenoviral vectors under conditions permissive for the infection of the cells, culturing the infected cells to replicate the adenoviral vectors, and harvesting the infected cells to obtain an adenoviral vector stock. A method of obtaining a synchronous culture of cells is also provided.