Abstract: Provided herein is a conditionally-replicating serotype 5 adenovirus or adenoviral vector expressing a mutant E1A protein under control of a promoter that is responsive to hypoxia and inflammation and one or more immune modulators under control of a tumor-specific promoter. The adenovirus or adenoviral vector also comprises serotype 3 fiber and hexon proteins. Also provided is a method of inducing cytotoxicity in tumor cells using a composition containing the adenovirus or adenoviral vector.

Abstract: Provided herein is a conditionally-replicating serotype 5 adenovirus or adenoviral vector expressing a mutant E1A protein under control of a promoter that is responsive to hypoxia and inflammation and one or more immune modulators under control of a tumor-specific promoter. The adenovirus or adenoviral vector also comprises serotype 3 fiber and hexon proteins. Also provided is a method of inducing cytotoxicity in tumor cells using a composition containing the adenovirus or adenoviral vector.

Abstract: Disclosed are methods of transforming dendritic cells with a chimeric adenovirus-5 (Ad5). A chimeric adenovirus includes a fiber comprising a tail, a shaft and a knob, wherein the knob is a porcine knob, and a nucleic acid comprising a promoter operably linked to a heterologous sequence encoding an antigen peptide.

Abstract: Disclosed are methods of transforming dendritic cells with a chimeric adenovirus-5 (Ad5). A chimeric adenovirus includes a fiber comprising a tail, a shaft and a knob, wherein the knob is a porcine knob, and a nucleic acid comprising a promoter operably linked to a heterologous sequence encoding an antigen peptide.

Abstract: The present invention provides means to modify the tropism of recombinant adenoviral vectors using genetic methods to alter the adenoviral fiber cell-binding protein. The present invention generates an adenovirus with modified fiber gene such that novel tropism is achieved. This recombinant adenovirus has a fiber gene modified in the HI loop domain.

Abstract: Human anti-epidermal growth factor receptor (EGFR) single-chain antibodies (scFvs) were isolated from a human IgM phage display library using purified epidermal growth factor receptor as antigen. Two isolates with different amino acid sequences were identified by ELISA as epidermal growth factor receptor-specific. The scFvs bind to the full length epidermal growth factor receptor and the truncated and/or mutated epidermal growth factor receptor on human cells. These anti-EGFR-scFvs are useful as therapeutic and/or diagnostic agents.

Abstract: The present invention describes recombinant adenoviral vectors modified by incorporating targeting ligands or label into viral capsid or structural proteins. In one embodiment, single-chain antibody was introduced into the minor capsid proteins pIIIa or pIX so that the adenoviral vector can be targeted to a particular cell type. In another embodiment, there is provided a noninvasive imaging strategy useful for monitoring the replication and spread of conditionally replicative adenoviral vectors. Viral structural proteins such as pIX capsid protein, core proteins mu, V and VII were expressed as fusion protein with a fluorescent label. Once incorporated into the virions, detection of the structural fusion protein label would indicate the localization of the disseminated viral progeny. The detected fluorescent signals also closely correlate with the level of viral replication and progeny production.

Abstract: The present invention provides a CD40-targeted gene delivery system and a CD40-targeted recombinant adenoviral vector for genetic manipulation of dendritic cells and B cells. Also provided are methods of using this enhanced gene delivery to immune system cells and therefore, enhancing dendritic cell-based immunotherapy.

Abstract: A modified adenovirus capable of overcoming the problem of low level of coxsackle-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to mutations in E1a or E1b genes.

Abstract: The utility of adenovirus vectors (Ad) for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural conflicts between the fiber and the targeting ligand. The present invention presents a strategy to derive an Ad vector with enhanced targeting potential by a radical replacement of the fiber protein in the Ad capsid with a chimeric molecule containing a heterologous trimerization motif and a receptor-binding ligand.

Abstract: A modified adenovirus capable of overcoming the problem of low level of coxsackie-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to specific promoter control or mutations in E1a or E1b genes.

Abstract: One major problem with adenovirus gene therapy has been the T-cell mediated immune response elicited by inoculation of adenovirus, which leads to rapid clearance of the virus and loss of transgene expression. In the instant invention, the immune response to a virus is prevented by pre-treatment with adenovirus, adenoassociated virus or herpes virus infected antigen-presenting cell (APC) expressing Fas ligand with induced T-cell tolerance. Administration of AdCMVLacZ after tolerance resulted in prolonged expression of LacZ in tolerized animals compared to control treated animals. In control, but not tolerized animals, there was proliferation of CD3+T-cell in the spleen in response to AdCMVLacZ treatment. Tolerance induction is also indicated by decreased production of interferon-&ggr; and IL-2 by peripheral T-cells isolated from treated animals after stimulation with the adenovirus infected APCs.

Abstract: The present invention describes recombinant adenoviral vectors modified by incorporating targeting ligands or label into viral capsid or structural proteins. In one embodiment, single-chain antibody was introduced into the minor capsid proteins pIIIa or pIX so that the adenoviral vector can be targeted to a particular cell type. In another embodiment, there is provided a noninvasive imaging strategy useful for monitoring the replication and spread of conditionally replicative adenoviral vectors. Viral structural proteins such as pIX capsid protein, core proteins mu, V and VII were expressed as fusion protein with a fluorescent label. Once incorporated into the virions, detection of the structural fusion protein label would indicate the localization of the disseminated viral progeny. The detected fluorescent signals also closely correlate with the level of viral replication and progeny production.

Abstract: Human anti-epidermal growth factor receptor (EGFR) single-chain antibodies (scFvs) were isolated from a human IgM phage display library using purified epidermal growth factor receptor as antigen. Two isolates with different amino acid sequences were identified by ELISA as epidermal growth factor receptor-specific. The scFvs bind to the full length epidermal growth factor receptor and the truncated and/or mutated epidermal growth factor receptor on human cells. These anti-EGFR-scFvs are useful as therapeutic and/or diagnostic agents.

Abstract: Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g.

Abstract: The present invention provides a strategy that allows for selective switching off of both transgene and viral gene expression in tissues where such expression is undesirable. The present invention employs a vector containing a tissue specific promoter that drives expression of Cre recombinase gene in tissue where transgene expression is undesirable. As a result of Cre recombinase expression, the same or another vector that expresses the transgene in that tissue will be cut by the action of the Cre recombinase into several pieces due to LoxP sites that are strategically placed within the vector backbone. Consequently, unwanted transgene as well as viral gene expression are prevented.

Abstract: The present invention provides a method of inducing an immune response in a non-invasive mode, comprising the step of: contacting skin of an individual in need of such treatment topically by applying to said skin an immunologically effective concentration of a genetic vector encoding a gene of interest. Also provided is a method of inducing an anti-tumor immune response in an animal in need of such treatment, comprising the step of: contacting skin of said animal topically by applying to said skin an immunologically effective concentration of a vector encoding a gene which encodes an antigen which induces an anti-tumor effect in said animal following administration. The genetic vector may include adenovirus recombinants, DNA/adenovirus complexes, DNA/liposome complexes, or any other vectors capable of expressing transgenes. Topical application of geneticvectors may preferably include a device as designed therein.

Abstract: Human anti-epidermal growth factor receptor (EGFR) single-chain antibodies (scFvs) were isolated from a human IgM phage display library using purified epidermal growth factor receptor as antigen. Two isolates with different amino acid sequences were identified by ELISA as epidermal growth factor receptor-specific. The scFvs bind to the full length epidermal growth factor receptor and the truncated and/or mutated epidermal growth factor receptor on human cells. These anti-EGFR-scFvs are useful as therapeutic and/or diagnostic agents.

Abstract: The present invention relates to gene therapy. In particular, therapeutic agents, therapeutic gene products, and compositions are disclosed. Various systems and methods useful in targeting and delivering non-native nucleotide sequences to specific cells are disclosed, wherein virus-antibody-ligand conjugates are used to facilitate targeting and delivery.

Abstract: One major problem with adenovirus gene therapy has been the T-cell mediated immune response elicited by inoculation of adenovirus, which leads to rapid clearance of the virus and loss of transgene expression. In the instant invention, the immune response to a virus is prevented by pre-treatment with adenovirus, adenoassociated virus or herpes virus infected antigen-presenting cell (APC) expressing Fas ligand with induced T-cell tolerance. Administration of AdCMVLacZ after tolerance resulted in prolonged expression of LacZ in tolerized animals compared to control treated animals. In control, but not tolerized animals, there was proliferation of CD3+ T-cell in the spleen in response to AdCMVLacZ treatment. Tolerance induction is also indicated by decreased production of interferon-&ggr; and IL-2 by peripheral T-cells isolated from treated animals after stimulation with the adenovirus infected APCs.