METHODS OF PREPARATION AND USE OF RECOMBINANT ADENOVIRAL VECTORS

摘要

The present invention describes novel methods of constructing recombinant adenoviral vectors capable of expressing human cDNAs, such as wild-type p53, WAF1/Cip1/p21, p27/kip1, E. coli cytosine deaminase, wild-type p16, TAM 67 (a jun/fos dominant negative mutant) and B7-1 and B7-2. The invention further provides methods of inhibiting the proliferation of cells, inhibiting the cell cycle of proliferating cells, and methods for the eradication of cells, especially cancer and diseased cells, by infecting the cells with a recombinant adenovirus vector capable of expressing human cDNAs. Compositions and methods of the invention are suitable for treatment of a subject afflicted with a tumor wherein the cells of the tumor, for example, lack the wild-type p53 allele and/or possess a mutated p53 gene. The invention additionally provides a method for the use of adenoviral vectors in the treatment of cancer cells, such as lung cancer and breast cancer cells. The invention further provides methods for the use of adenoviral vectors in cancer gene therapy as a mechanism for purging bone marrow cells of contaminanting tumor cells, for eradicating cancer cells, and for preventing development of cancer cells and tumors.