Abstract: Replication-competent adenoviral vectors comprising an EBV-specific transcriptional regulatory element (TRE) operably linked to a gene required for adenovirus replication are provided. By providing for transcriptional initiating regulation dependent upon transcription factors that are only active in specific, limited cell types, virus replication can be restricted to particular target cells. The modified adenovirus may be used as a vehicle for introducing new genetic capability, particularly associated with cytotoxicity for treating neoplasia.

Abstract: Colon cancer specific promoter sequences and adenovirus vehicles are provided. By providing for transcriptional initiating regulation dependent upon transcription factors that are only active in specific, limited cell types, virus replication will be restricted to the target cells. The modified adenovirus may be used as a vehicle for introducing new genetic capability, particularly associated with cytotoxicity for treating neoplasia.

Abstract: Compositions and methods for enhancing introduction of therapeutic agents into the bladder epithelium for the treatment of bladder diseases and disorders such as bladder cancer are described. According to one method, the luminal surface of the bladder is contacted with a composition comprising a bladder enhancer and a therapeutic agent for the treatment of the bladder disease. According to an alternative method, the luminal surface of the bladder is first contacted with a pretreatment composition comprising a bladder enhancer and subsequently contacted with a composition comprising a therapeutic agent for the treatment of the bladder disease. The transduction enhancing agent can be a mono-, di-, or poly-saccharide having a lipophilic substituent such as n-dodecyl-?-D-maltoside (DDM). Compositions comprising a transduction enhancing agent and a therapeutic agent for the treatment of a bladder disease are also described.

Abstract: The present invention provides adenoviral vectors comprising cell status-specific transcriptional regulatory elements which confer cell status-specific transcriptional regulation on an adenoviral gene. A “cell status” is generally a reversible physiological and/or environmental state. The invention further provides compositions and host cells comprising the vectors, as well as methods of using the vectors.

Abstract: The invention generally relates to targeted gene therapy using recombinant vectors and particularly adenovirus vectors. The invention specifically relates to replication-conditional vectors and methods for using them. Such vectors are able to selectively replicate in a target tissue to provide a therapeutic benefit from the presence of the vector per se or from heterologous gene products expressed from the vector and distributed throughout the tissue. In such vectors, a gene essential for replication is placed under the control of a heterologous tissue-specific transcriptional regulatory sequence. Thus, replication is conditioned on the presence of a factor(s) that induces transcription or the absence of a factor(s) that inhibits trancription of the gene by means of the transcriptional regulatory sequence with this vector; therefore, a target tissue can be selectively treated.

Abstract: A cell delivery system and method for delivering cells locally to a tissue, body cavity, or joint is described. The cell delivery system comprises a catheter configured to deliver stem cells in a pressure controlled manner. The catheter may comprise an inner bladder and an outer perforated bladder. The inner bladder may be expanded through the use of a pressure conduit in order to deploy a stent. Cells, such as endothelial cells derived from adipose tissue, may be introduced between the inner and outer bladder. The inner bladder may be further expanded in order to exert pressure on the outer perforated bladder to advance the stems cells though the apertures of the outer bladder. The inner bladder may remain pressurized to hold the outer bladder against the vessel wall, thereby directing the stem cells to specific target sites. The system may be used to deliver stem cells with or without other therapeutic agents. The system may be used with or without a stent.

Abstract: A method and system for managing a direct repair program includes receiving one or more estimates of repair cost from one or more shops and determining which of the received one or more estimates are in compliance with one or more requirements. The one or more compliant estimates from the one or more shops and stored feedback on the one or more shops associated with the compliant estimates are provided to the source of the claim. A selection of one of the compliant estimates based on the compliant estimates and the stored feedback is received and the claim is awarded to the selected one of the one or more shops.

Abstract: Cellular compositions and methods for inducing an immune response to tumor cells are described. The cellular compositions include a tumor antigen and cells that have been modified to express a cytokine and one or more of a tumor antigen, anti-CTLA4 antibody and an additional cytokine. The cellular compositions find utility in methods for treating cancer.

Abstract: Replication-competent adenovirus vectors specific for cells which allow a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise an adenoviral gene under control of a transcriptional regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells.

Abstract: A messaging server application system handles message creation, receipt, and response for any sort of digitizable message in any format. It typically operates as a core application and application infrastructure in a communications network or networks in the multiple sender, receiver and user modes of the same or varying design and operational characteristics. The system uses an application architecture organized using a set of ten loosely-coupled subsystems falling into three general functional groups: interface/connector subsystems, core subsystems, and storage subsystems. The interface/connector subsystems include voice, data and multimedia gateways as well as message connectors and a multimodal authenticator. The core subsystems include a multimedia messaging bus, an independent metadata messaging bus, and a content transformer. The storage subsystem can include various storage subsystems.

Abstract: Single AAV vector constructs for regulated expression of an immunoglobulin molecule or fragment thereof and methods of making and using the same are described. The AAV vectors comprise a regulated promoter operably linked to the coding sequence for a first and second immunoglobulin coding sequence, a sequence encoding a self-processing cleavage site between the coding sequence for the first and second immunoglobulin coding sequence and a additional proteolytic cleavage site, which provides a means to remove the self processing peptide sequence from an expressed immunoglobulin molecule or fragment thereof. The vector constructs find utility in enhanced production of biologically active immunoglobulins or fragments thereof in vitro and in vivo.

Abstract: The present invention in all of its associated aspects provides improved methods and compositions for treating cancer in a mammal based on the sequential administration of the combination of a cytokine-expressing cancer immunotherapy composition and at least one tyrosine kinase inhibitor, wherein administration of the combination results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cancer immunotherapy composition or at least one tyrosine kinase inhibitor as a monotherapy.

Abstract: The invention provides methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

Abstract: A messaging server application system handles message creation, receipt, and response for any sort of digitizable message in any format. It typically operates as a core application and application infrastructure in a communications network or networks in the multiple sender, receiver and user modes of the same or varying design and operational characteristics. The system uses an application architecture organized using a set of ten loosely-coupled subsystems falling into three general functional groups: interface/connector subsystems, core subsystems, and storage subsystems. The interface/connector subsystems include Voice, Data and Multimedia Gateways as well as Message Connectors and aMultimodal Authenticator. The core subsystems include a Multimedia Messaging Bus, an independent Metadata Messaging Bus, and a Content Transformer. The Storage Subsystem can include various Storage Subsystems.

Abstract: The present invention provides novel, isolated, tumor-associated antigens, and methods for identifying such antigens in a biological sample, and of screening for the presence of such an antigen in a biological specimen, wherein the tumor antigen identified reacts with serum from a subject treated with a vaccine comprising a cytokine and proliferation-incompetent tumor cells which express the tumor-associated antigen. Also provided are kits for carrying out the methods of the invention.

Abstract: Agents and methods for enhancing recombinant virus transduction in the bladder epithelium are described. A first method involves contacting the luminal surface of the bladder with a composition comprising a transduction enhancing agent and an oncolytic virus. Alternatively, the luminal surface of the bladder can be contacted first with a pretreatment composition comprising a transduction enhancing agent and, subsequently, with a composition comprising an oncolytic virus. Bladder treatment compositions comprising a transduction enhancing agent and an oncolytic virus are also described.

Abstract: The invention provides a novel retroviral packaging system, in which retroviral packaging plasmids and packagable vector transcripts are produced from high expression plasmids after stable or transient transfection in mammalian cells. High titers of recombinant retrovirus are produced in these transfected mammalian cells and can then transduce a mammalian target cell by cocultivation or supernatant infection. The methods of the invention include the use of the novel retroviral packaging plasmids and vectors to transduce primary human cells, including T cells and human hematopoietic stem cells, with foreign genes by cocultivation or supernatant infection at high efficiencies. The invention is useful for the rapid production of high titer viral supernatants, and to transduce with high efficiency cells that are refractory to transduction by conventional means.

Abstract: Recombinant lentiviruses and transfer vectors for transgene delivery as well as methods for gene therapy using such vectors are disclosed. The invention provides a third generation lentiviral packaging system and a set of vectors for producing recombinant lentiviruses, as well as novel tissue specific enhancer and promoter elements useful for optimizing liver specific transgene delivery. The transgene is preferably a blood clotting factor such as human factor IX (hFIX) or human factor VIII (hFVIII) and can be used for treatment of hemophilia.

Abstract: Lentiviral vectors modified at the 5? LTR or both the 5? and 3? LTR are useful in the production of recombinant lentivirus vectors (See the Figure). Such vectors can be produced in the absence of a functional tat gene. Multiple transformation of the host cell with the vector carrying the transgene enhances virus production. The vectors can contain inducible or conditional promoters.

Abstract: Adenovirus packaging cell lines for growth of an E1A/E1B deficient adenovirus that is substantially free of replication competent adenovirus (RCA) are provided. Methods for producing adenovirus substantially free of RCA are also provided, wherein the adenovirus is grown in a cell line containing coding sequences for adenovirus E1A and E1B, which are operably linked to promoters that lack polynucleotide sequences sharing substantial sequence identity with the native adenovirus E1A and E1B promoters.