Abstract: A non-human mammalian model of an autoimmune disorder co-expresses a major histocompatibility (MHC) class II-restricted T cell receptor (TCR) and a selected peptide that binds to the TCR. The selected peptide is selectively expressed by MHC class II positive antigen presenting cells (APC) of the mammal. Models with high penetrance of disease are those in which the selected peptide is a MHC class II-restricted T cell determinant that specifically binds with high affinity to the TCR. Models with low penetrance of disease are those in which the selected peptide binds with low affinity to the TCR. These models, which may be transgenic mammals, are used in method for identifying diagnostic and therapeutic markers and targets characteristic of an autoimmune disorder.
Type:
Application
Filed:
October 27, 2003
Publication date:
July 13, 2006
Applicant:
THE WISTAR INSTITUTE of ANATOMY and BIOLOGY
Abstract: Modifications of the peptide pyrrhocoricin permit the production of a variety of anti-bacterial or anti-fungal peptides having general formula R1-Asp-Lys-Gly-X-Y-Leu-Pro-Arg-Pro-Thr-Pro-Pro-Arg-Pro-Ile-Tyr-X?-Y?-R2 SEQ ID NO: 1 or multimeric compositions containing more than a single peptide of that formula. These peptides may be straight chain or cyclic peptides, and may contain one or more non-cleavable bonds. These peptides are characterized by anti-bacterial or anti-fungal activity and metabolic stability in mammalian serum. These peptides are useful in anti-bacterial or anti-fungal pharmaceutical compositions and for further drug development or identification of other antibiotic or anti-fungal compounds.
Type:
Grant
Filed:
June 21, 2000
Date of Patent:
March 21, 2006
Assignee:
The Wistar Institute of Anatomy and Biology
Abstract: Modifications of the peptide pyrrhocoricin permit the production of a variety of anti-bacterial or anti-fungal peptides having the general formula R1-Asp-Lys-Gly-X-Y-Leu-Pro-Arg-Pro-Thr-Pro-Pro-Arg-Pro-Ile-Tyr-X?-Y?-R2 [SEQ ID NO: 1] or multimeric compositions containing more than a single peptide of that formula. These peptides may be straight chain or cyclic peptides, and may contain one or more non-cleavable bonds. These peptides are characterized by anti-bacterial or anti-fungal activity and metabolic stability in mammalian serum. These peptides are useful in anti-bacterial or anti-fungal pharmaceutical compositions and for further drug development or identification of other antibiotic or anti-fungal compounds.
Type:
Application
Filed:
September 7, 2005
Publication date:
January 5, 2006
Applicant:
The Wistar Institute of Anatomy and Biology
Abstract: The present invention provides Bin2 sequences and proteins encoded thereby. Also provided are compositions and methods utilizing these sequences and proteins in the diagnosis and treatment of blood disorders, including hepatocarcinoma. Further provided are oligonucleotides derived from sequences encoding Bin2, as well as compositions and methods utilizing same for diagnostic and therapeutic purposes.
Type:
Application
Filed:
October 29, 2004
Publication date:
September 29, 2005
Applicant:
The Wistar Institute of Anatomy and Biology
Abstract: Compositions containing one or more peptido-mimetics or modified peptido-mimetics of a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier are useful for methods of reducing metastasis in a mammal and for inhibiting inflammatory response in a mammal. Particularly useful are embodiments in which the ligand is a Lewis antigen and/or the adhesion molecule is a selectin, e.g., E-selectin. Methods are disclosed for identifying peptido-mimetics of carbohydrate ligands, which may be involved in binding of tumor cells to other cells, such as endothelial cells.
Type:
Application
Filed:
March 16, 2005
Publication date:
August 18, 2005
Applicants:
The Wistar Institute of Anatomy and Biology, The Trustees of the University of Pennsylvania
Inventors:
Magdalena Blaszczyk-Thurin, Thomas Kieber-Emmons
Abstract: The present invention provides Bin2 sequences and proteins encoded thereby. Also provided are compositions and methods utilizing these sequences and proteins in the diagnosis and treatment of blood disorders, including hepatocarcinoma. Further provided are oligonucleotides derived from sequences encoding Bin2, as well as compositions and methods utilizing same for diagnostic and therapeutic purposes.
Type:
Grant
Filed:
February 25, 2002
Date of Patent:
December 14, 2004
Assignee:
The Wistar Institute of Anatomy and Biology
Abstract: TALL-104 cells, and other cytotoxic T cell lines, may be modified to increase the cytotoxicity thereof, to enhance growth properties, and/or to provide a preferred phenotype, e.g., expression of cell surface antigens, function, e.g., change in cytokine production profile, by culturing the cells in an effective amount of IL-15, optionally followed by gamma irradiation to halt proliferation.
Type:
Grant
Filed:
August 21, 2001
Date of Patent:
December 7, 2004
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Daniela Santoli, Giovanni Rovera, Alessandra Cesano
Abstract: Methods for treating cancer in a mammalian patient having cancer and a functional immune system, and for preventing recurrences of cancer following completion of cancer therapy, are described. The methods involve administration of a course of therapy with modified TALL-104 cells, without requiring the co-administration of an immunosuppressive agent.
Type:
Grant
Filed:
June 20, 1997
Date of Patent:
April 6, 2004
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Daniela Santoli, Giovanni Rovera, Alessandra Cesano
Abstract: A method of reducing immune response during gene therapy is provided which involves co-administration of the viral vector bearing a therapeutic transgene and a selected immune modulator capable of inhibiting the formation of neutralizing antibodies and/or CTL elimination of the vectors upon repeated administration.
Type:
Application
Filed:
November 27, 2001
Publication date:
November 27, 2003
Applicants:
The Trustees of the University of Pennsylvania, The Wistar Institute of Anatomy and Biology
Inventors:
James M. Wilson, Yiping Yang, Giorgio Trinchieri
Abstract: The present invention describes novel soluble variants of type I membrane protein GA733-2 and methods of making and using them. In addition, the present invention describes a method of converting type I membrane proteins into secretory proteins which may be used for active immunotherapy against carcinomas and as reagents in the detection of GA733-2 expression on tumor cells.
Type:
Grant
Filed:
March 30, 1995
Date of Patent:
November 11, 2003
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Alban J. Linnenbach, Hilary Koprowski, Dorothee Herlyn
Abstract: The present invention provides Bin1 genomic sequences and proteins encoded thereby. Also provided are compositions and methods utilizing these sequences and proteins in the diagnosis and treatment of cancers and hyperplastic disease states. Further provided are oligonucleotides derived from sequences encoding Bin1, as well as compositions and methods utilizing same for diagnostic and therapeutic purposes.
Type:
Application
Filed:
April 16, 2002
Publication date:
September 4, 2003
Applicant:
The Wistar Institute of Anatomy and Biology
Inventors:
George C. Prendergast, Daitoku Sakamuro
Abstract: A method for identifying a compound that has a biocidal effect against a selected organism involves screening from among known or unknown peptide or non-peptide molecules, a test molecule that binds selectively to a target sequence of a multi-helical lid of a heat shock protein of the organism. The binding of the test compound inhibits the protein folding activity of the protein. A specific embodiment of such a method is useful for identifying or designing a pharmaceutical or veterinary biocidal or antibiotic compound, preferably a pathogen and/or strain-specific compound. For this purpose, the compound does not bind to a heat shock protein that is homologous to the mammalian subject to be treated with the compound. Screening methods can encompass direct binding or competitive assays. Molecules or compounds identified by these methods are employed as biocides for pharmaceutical, veterinary, pesticide, insecticide and rodenticide uses, among others.
Type:
Application
Filed:
July 19, 2002
Publication date:
June 12, 2003
Applicant:
The Wistar Institute of Anatomy and Biology
Abstract: The present invention describes novel soluble variants of type I membrane protein GA733-2 and methods of making and using them. In addition, the present invention describes a method of converting type I membrane proteins into secretory proteins which may be used for active immunotherapy against carcinomas and as reagents in the detection of GA733-2 expression on tumor cells.
Type:
Application
Filed:
November 19, 2002
Publication date:
June 5, 2003
Applicant:
The Wistar Institute of Anatomy and Biology
Inventors:
Alban J. Linnenbach, Hilary Koprowski, Dorothee Herlyn
Abstract: Two stable cytolytic T lymphocyte cell lines and a clone are established from two primary colorectal carcinoma patients. A method for generating stable anti-colorectal carcinoma CTL clones and cell lines includes the step of stimulating the lymphocytes of a patient with minimal or no clinical evidence of colorectal carcinoma in culture with irradiated autologous primary colorectal carcinoma tumor cells, interleukin-2, and either autologous lymphocytes or autologous EBV-B cells.
Type:
Grant
Filed:
October 18, 1999
Date of Patent:
March 4, 2003
Assignee:
The Wistar Institute of Anatomy and Biology
Abstract: A method for repairing defects and inducing vascularization in mammalian tissue, preferably skin, involves administering to the tissue a recombinant replication defective virus, preferably adenovirus, carrying a selected growth factor gene, preferably VEGF or PDGF, under operative control of regulatory sequences which direct the expression of the growth factor(s). Also provided is a method for infecting a tissue to be transplanted with such recombinant adenoviruses prior to transplantation and, as a composition, an infected culture of human tissue to be transplanted which is infused with a selected growth factor prior to transplantation. Screening methods for the treatment of angiogenic disorders, e.g., hemangiomas and cancers, also employ an animal model on which is engrafted a full thickness human tissue infused with a growth factor.
Type:
Grant
Filed:
August 25, 1999
Date of Patent:
November 26, 2002
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Meenhard Herlyn, Mark Nesbit, Kapaettu Satyamoorthy
Abstract: Novel DNA molecules for in vitro and in vivo expression of HCMV gB, gB transmembrane deleted derivatives, pp65, pp150, and IE-exon-4 proteins are described. Preferably, the molecules are plasmids. Also described are methods of using these DNA molecules to induce immune responses to HCMV, and the use of a plasmid of the invention to prime immune responses to HCMV vaccines.
Type:
Grant
Filed:
January 19, 1999
Date of Patent:
September 10, 2002
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Eva Gonczol, Klara Berencsi, Csaba Kari
Abstract: The present invention provides Bin1 genomic sequences and proteins encoded thereby. Also provided are compositions and methods utilizing these sequences and proteins in the diagnosis and treatment of cancers and hyperplastic disease states. Further provided are oligonucleotides derived from sequences encoding Bin1, as well as compositions and methods utilizing same for diagnostic and therapeutic purposes.
Type:
Grant
Filed:
December 3, 1999
Date of Patent:
June 25, 2002
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
George C. Prendergast, Daitoku Sakamuro
Abstract: Modified p53 tetramerization domains which do not hetero-oligomerize with native p53 tetramerization domains are described. These modified p53 tetramerization domains have one or more of the following substitutions in the region of residues 325 to 355 of human p53: Leu330 substituted with Phe; Met340 substituted with Phe; Ala347 substituted with Ile; Leu348 substituted with Met; Ala353 substituted with Leu; Gln354 substituted with Leu; Ala355 substituted with Asp. Also described are p53 proteins containing these modified p53 tetramerization domains linked to a p53 DNA binding domain. These proteins and the nucleic acid sequences encoding them, are useful in ameliorating conditions associated with inappropriate p53 function.
Type:
Grant
Filed:
May 5, 1999
Date of Patent:
May 14, 2002
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Thanos D. Halazonetis, Elena S. Stavridi
Abstract: Methods for enhancing the therapeutic and adjuvant use of IL-12 by reducing unwanted transient immunosuppression caused by IL-12 or by high doses thereof involve co-administering IL-12 with an effective amount of an agent that inhibits or neutralizes nitric oxide (NO) in vivo. Enhanced vaccine therapy involves co-administering the IL-12 adjuvant, a selected vaccine antigen and the NO inhibiting/neutralizing agent. Additionally, the toxicity of IL-12 treatment may be reduced by co-administering IL-12 with an effective amount of the NO inhibiting or neutralizing agent. A therapeutic composition characterized by reduced toxicity in mammals contains IL-12, preferably a low dose thereof, and an NO inhibiting or neutralizing agent in a pharmaceutically acceptable carrier. A vaccine composition contains an effective adjuvanting amount of IL-12, an effective amount of an NO inhibiting or neutralizing agent, and an effective protective amount of a vaccine antigen in a pharmaceutically acceptable carrier.
Type:
Grant
Filed:
September 13, 1999
Date of Patent:
April 23, 2002
Assignees:
The Wistar Institute of Anatomy and Biology, The Trustees of the University of Pennsylvania
Inventors:
Giorgio Trinchieri, William M. F. Lee, Holly Koblish
Abstract: A method of reducing immune response to a viral vector containing a selected transgene is provided. The method involves co-administration of the viral vector and a selected immune modulator capable of inhibiting the formation of neutralizing antibodies and/or CTL elimination of the vectors upon repeated administration.
Type:
Grant
Filed:
September 28, 1999
Date of Patent:
April 16, 2002
Assignees:
The Trustees of the University of Pennsylvania, The Wistar Institute of Anatomy and Biology
Inventors:
James M. Wilson, Yiping Yang, Giorgio Trinchieri