Recombinant adenoviral vector and method of use
First Claim
1. A method for obtaining expression of a tumor suppressor gene in a tumor cell in a mammal in vivo, wherein the tumor cell is caused by the absence of a tumor suppressor gene or the presence of a pathologically mutated tumor suppressor gene, the method comprising:
- contacting the tumor cell with an effective amount of a replication-deficient recombinant adenovirus expression vector comprising;
a) a partial or total deletion of a protein IX-encoding DNA sequence, and b) a gene encoding a foreign protein having a tumor suppressive function, wherein said contacting comprises intratumoral, peritumoral or intravesicular injection of the recombinant adenenovirus expression vector under suitable conditions such that the foreign protein is expressed in the tumor cell.
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Abstract
This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine dinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective.)
15 Citations
32 Claims
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1. A method for obtaining expression of a tumor suppressor gene in a tumor cell in a mammal in vivo, wherein the tumor cell is caused by the absence of a tumor suppressor gene or the presence of a pathologically mutated tumor suppressor gene, the method comprising:
contacting the tumor cell with an effective amount of a replication-deficient recombinant adenovirus expression vector comprising;
a) a partial or total deletion of a protein IX-encoding DNA sequence, and b) a gene encoding a foreign protein having a tumor suppressive function, wherein said contacting comprises intratumoral, peritumoral or intravesicular injection of the recombinant adenenovirus expression vector under suitable conditions such that the foreign protein is expressed in the tumor cell.- View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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2. A method of inhibiting the proliferation of a tumor cell in a mammal, wherein the tumor cell is caused by the absence of a tumor suppressor gene or the presence of a pathologically mutated tumor suppressor gene, the method comprising:
administering to the mammal an effective amount of a replication-deficient recombinant adenovirus expression vector comprising;
a) a partial or total deletion of a protein IX-encoding DNA sequence; and
b) a gene encoding a foreign functional protein having a tumor suppressive function under suitable conditions to the mammal, wherein said administering comprises intratumoral, peritumoral or intravesicular injection of the replication-deficient recombinant adenenovirus vector under suitable conditions such that the foreign functional protein is expressed in the tumor cell.
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16. A method for obtaining expression of a suicide protein in a cell, the method comprising administering to the cell an effective amount of a recombinant adenovirus expression vector comprising:
- a) a partial or total deletion of a protein IX-eneoding DNA sequence, and b) a gene encoding a suicide protein, wherein an mRNA encoding the suicide protein is produced by the cell.
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17. A method for reducing the proliferation of a tumor cell in a mammal, the method comprising administering under suitable conditions an effective amount of an adenoviral expression vector comprising:
- a) a partial or total deletion of a protein IX-encoding DNA sequence, and b) a gene encoding a suicide protein or a biologically active fragment thereof; and
a therapeutic agent that in the presence of the suicide protein is toxic to the tumor cell. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
- a) a partial or total deletion of a protein IX-encoding DNA sequence, and b) a gene encoding a suicide protein or a biologically active fragment thereof; and
Specification