The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides gene expression profiles associated with solid tumor stem cells, as well as novel stem cell cancer markers useful for the diagnosis, characterization, and treatment of solid tumor stem cells.

Compositions and methods for treating and diagnosing cancer

Recurrent gene fusions of androgen regulated genes and ETS family member genes in prostate cancer are described. Compositions and methods having utility in prostate cancer diagnosis, research, and therapy are also provided.

Recurrent gene fusions in prostate cancer

The invention provides improved methods and products based on adenoviral materials which can advantageously be used in for instance gene therapy. In one aspect an adenoviral vector is provided which has no overlap with a suitable packaging cell line which is another aspect of invention. This combination excludes the possibility of homologous recombination, thereby excluding the possibility of the formation of replication competent adenovirus. In another aspect an adenovirus based helper construct which by its size is incapable of being encapsidated. This helper virus can be transferred into any suitable host cell making it a packaging cell. Further a number of useful mutations to adenoviral based materials and combinations of such mutations are disclosed, which all have in common the safety of the methods and the products, in particular avoiding the production of replication competent adenovirus and/or interference with the immune system. Further a method of intracellular amplification is provided.

Packaging systems for human recombinant adenovirus to be used in gene therapy

A virus, or virus-like particle, derived from a virus or virus-like particle having a receptor for a host cell comprising a modified binding specificity conferred by a binding moiety allowing the virus or virus-like particle to bind to a target cell characterised in that the said host cell receptor is modified or absent so that the virus or virus-like particle is substantially incapable of binding the said host cell are disclosed. An adenovirus or influenza virus or vaccinia virus, or a replication defective derivative of any of these, characterized in that the virus has a modified binding specificity conferred by a binding moiety allowing the virus to bind to a target cell are disclosed. Suitable binding moieties include monoclonal antibodies, ScFvs, dAbs and minimal recognition units. The use of at least some of these as delivery vehicles for genes to target cells in the fields of gene therepy and cancer treatment are disclosed.

Virus with modified binding moiety specific for the target cells

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

Isolation and use of solid tumor stem cells

The present invention provides multiply deficient adenoviral vectors and complementing cell lines. Also provided are recombinants of the multiply deficient adenoviral vectors and a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such recombinants.

Stocks of recombinant, replication-deficient adenovirus free of replication-competent adenovirus

A method of introducing an adenovirus into a cell that comprises a particular cell surface binding site, as well as a chimeric adenovirus penton base protein and recombinant adenoviral vector comprising the chimeric adenovirus penton base protein for use in the method, are provided.

Adenoviral-mediated cell targeting commanded by the adenovirus penton base protein

A recombinant adenovirus comprising a chimeric penton base protein, which includes a nonpenton base sequence, and a therapeutic gene, a method of gene therapy involving the use of such adenovirus, and adenoviral transfer vectors for the generation of such recombinant adenovirus are provided.

Penton base protein and methods of using same

Local adenoviral-mediated inducible nitric oxide synthase gene transfer inhibits neointimal formation in the porcine coronary stented model

The present invention provides a dual selection cassette (DSC) comprising first and second DNA segments having homology to a eukaryotic viral vector, positive and negative selection genes, each operably linked to their own promoter, and one or more unique restriction enzyme sites (URES) or site-directed homologous recombination sites. The present invention also provides a plasmid, pN/P, comprising an independent positive selection marker gene, an origine of replication, and a dual selection cassette. The dual selection cassette and pN/P plasmid can be used to produce eukaryotic gene transfer vectors without requiring temporally-linked double recombination events or the use of specialized bacterial strains that allow the replication of plasmids comprising defective origins of replication. This method usefully increases the ratio of desired to undesired plasmid and vector constructs. Additionally, this invention provides a method for the creation of eukaryotic viral vector libraries.

Plasmids for construction of eukaryotic viral vectors

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