Patents by Inventor Lee M. Nadler
Lee M. Nadler has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 8026224Abstract: Tumor cells modified to express a T cell costimulatory molecule are disclosed. In one embodiment, the costimulatory molecule is a CD28/CTLA4 ligand, preferably a B lymphocyte antigen B7. The tumor cells of the invention can be modified by transfection with nucleic acid encoding a T cell costimulatory molecule, by using an agent which induces or increases expression of a T cell costimulatory molecule on the tumor cell surface or by coupling a T cell costimulatory molecule to the tumor cell surface. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating-a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor.Type: GrantFiled: December 20, 2005Date of Patent: September 27, 2011Assignees: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard College, University of MarylandInventors: Suzanne Ostrand-Rosenberg, Sivasubramanina Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
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Patent number: 7955845Abstract: The invention relates to antigen-presenting cells having specificity against a selected antigen and methods for making the cells. The invention also relates to a method of selecting efficient antigen-presenting cells using reporter fusion constructs. The highly efficient antigen-presenting cells of the invention will provide a therapeutic strategy of modulating immune responses for a variety of diseases.Type: GrantFiled: May 20, 2004Date of Patent: June 7, 2011Assignee: Dana Farber Cancer Institute, Inc.Inventors: Naoto Hirano, Marcus Butler, Lee M. Nadler
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Patent number: 7851591Abstract: The invention provides methods for conducting cancer immunotherapy and diagnosis using universal tumor associated antigens, such as the telomerase catalytic subunit (hTERT), and methods for identifying and characterizing universal tumor associated antigens.Type: GrantFiled: October 29, 1999Date of Patent: December 14, 2010Assignee: Dana Farber Cancer Institute, Inc.Inventors: Lee M. Nadler, William C. Hahn, Joachim L. Schultze, Robert H. Vonderheide
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Patent number: 7700102Abstract: Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferation are disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.Type: GrantFiled: December 16, 2002Date of Patent: April 20, 2010Assignees: Dana-Farber Cancer Institute, Institut National de la Sante et de la Recherche Medicale (INSERM)Inventors: Kathryn T. Hall, Gordon J. Freeman, Joachim L. Schultze, Vassiliki A. Boussiotis, Lee M. Nadler, Laurence Boumsell, Armand Bensussan
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Patent number: 7619078Abstract: Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.Type: GrantFiled: October 26, 2006Date of Patent: November 17, 2009Assignees: Dana-Farber Cancer Institute, Inc., The Brigham And Women's Hospital, Inc.Inventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
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Patent number: 7592007Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.Type: GrantFiled: December 9, 2003Date of Patent: September 22, 2009Assignees: Dana-Farber Cancer Institute, Inc., Genetics Institute, LLCInventors: John G. Gribben, Gordon J. Freeman, Lee M. Nadler, Paul Rennert, Cindy L. Jellis, Edward Greenfield, Gary S. Gray
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Patent number: 7459544Abstract: Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.Type: GrantFiled: May 2, 2003Date of Patent: December 2, 2008Assignees: Genetics Institute, LLC, Dana-Farber Cancer InstituteInventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray
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Patent number: 7385023Abstract: The invention provides methods for conducting cancer immunotherapy and diagnosis using cytochrome P450 1B1 and peptide fragments thereof.Type: GrantFiled: November 15, 2000Date of Patent: June 10, 2008Assignees: Trustees of Boston University, Dana Farber Cancer Institute, Inc.Inventors: Joachim L. Schultze, Robert H. Vonderheide, David Sherr, Lee M. Nadler, Britta Maecker, Michael Bergwelt-Baildon
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Patent number: 7195758Abstract: We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1×103 to 1×104 fold in 2 weeks or 1×105 to 1×106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGF?.Type: GrantFiled: July 1, 2002Date of Patent: March 27, 2007Assignee: Dana-Farber Cancer Institute, Inc.Inventors: Joachim L. Schultze, Gordon J. Freeman, John G. Gribben, Lee M. Nadler
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Patent number: 7153934Abstract: Structural forms of T cell costimulatory polypeptides are described. These forms comprise an alternative structural domain (i.e., a structural domain having an amino acid sequence which differs from a known amino acid sequence) or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory polypeptides or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory polypeptide of the invention contains an alternative cytoplasmic domain. In another embodiment, the T cell costimulatory polypeptide of the invention contains an alternative signal peptide domain or has an immunoglobulin variable region-like domain deleted.Type: GrantFiled: September 24, 2001Date of Patent: December 26, 2006Assignees: Dana-Faber Cancer Institute, Inc., Brigham and Women's HospitalInventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
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Patent number: 6824779Abstract: The present invention relates to, inter alia, methods for inhibiting the interaction of the B-lymphocyte antigen, B7-2, with its natural ligand on the surface of an immune cell are disclosed. The methods comprise contacting the immune cell with an agent which inhibits B7-2 binding with its natural ligand, to thereby inhibit the interaction. Examples of such agents are provided, and include a soluble form of B7-2, an antibody that recognized B7-2. The method may also include contacting the immune cell with an agent that blocks the interaction of B7-1 with its natural ligand. Further, the method may include contacting the immune cell with an immunomodulating agent, for example, an antibody reactive with CD28, an antibody reactive with CTLA4, an antibody reactive with a cytokine, a CTLA4Ig fusion protein, a CD28Ig fusion protein, and an immunosuppressive drug. Both in vivo and in vitro applications of the method are disclosed.Type: GrantFiled: October 22, 1999Date of Patent: November 30, 2004Assignees: Dana-Farber Cancer Institute, Inc., Genetics Institute, LLCInventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray
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Therapeutic compositions for inhibiting the interactions of B7-1 and B7-2 with their natural ligands
Publication number: 20040230051Abstract: Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.Type: ApplicationFiled: May 2, 2003Publication date: November 18, 2004Inventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray -
Publication number: 20040202650Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.Type: ApplicationFiled: December 9, 2003Publication date: October 14, 2004Inventors: John G. Gribben, Gordon J. Freeman, Lee M. Nadler, Paul D. Rennert, Cindy L. Jellis, Edward Greenfield, Gary S. Gray
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Publication number: 20040192899Abstract: Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.Type: ApplicationFiled: August 18, 2003Publication date: September 30, 2004Applicants: BRIGHAM AND WOMENS HOSPITAL, Dana-Farber Cancer Institute, Inc.Inventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
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Patent number: 6723705Abstract: Tumor cells modified to express one or more T cell costimulatory molecules are disclosed. Preferred costimulatory molecules are B7-2 and B7-3. The tumor cells of the invention can be modified by transfection with nucleic acid encoding B7-2 and/or B7-3, by using an agent which induces or increases expression of B7-2 and/or B7-3 on the tumor cell or by coupling B7-2 and/or B7-3 to the tumor cell. Tumor cells modified to express B7-2 and/or B7-3 can be further modified to express B7. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor.Type: GrantFiled: December 7, 1998Date of Patent: April 20, 2004Assignee: Gentics Institute, Inc.Inventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray
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Patent number: 6719972Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific. T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.Type: GrantFiled: June 3, 1994Date of Patent: April 13, 2004Assignees: Repligen Corporation, Dana-Farber Cancer InstituteInventors: John G. Gribben, Gordon J. Freeman, Lee M. Nadler, Paul Rennert, Cindy L. Jellis, Edward Greenfield, Gary S. Gray
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Publication number: 20040037808Abstract: When stimulated through the T cell receptor(TCR)/CD3 complex without requisite costimulation through the CD28/B7 interaction, T cells enter a state of antigen specific unresponsiveness or anergy. This invention is based, at least in part, on the discovery that signaling though a common cytokine receptor &ggr; chain (e.g., interleukin-2 receptor, interleukin-4 receptor, interleukin-7 receptor) prevents the induction of T cell anergy. This &ggr; chain has been found to be associated with a JAK kinase having a molecular weight of about 116 kD (as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis) and signaling through the &ggr; chain induces phosphorylation of the JAK kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor &ggr; chain are disclosed.Type: ApplicationFiled: June 10, 2003Publication date: February 26, 2004Applicant: Dana-Farber Cancer InstituteInventors: Vassiliki A. Boussiotis, Lee M. Nadler
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Patent number: 6653444Abstract: Isolated nucleic acid molecules encoding a B cell activation antigen, B7, are provided. In one embodiment, the nucleic acid molecules are DNA sequences. The DNA sequences of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also provided are host cells transformed to produce proteins or peptides encoded by the DNA molecules of the present invention and purified proteins and peptides which comprise at least a portion of the B cell activation antigen. The proteins and peptides comprise at least a portion of the mature form of the B7 activation antigen and preferably comprise a soluble form of the B7 protein.Type: GrantFiled: May 30, 1995Date of Patent: November 25, 2003Assignee: Dana-Farber Cancer Institute, Inc.Inventors: Gordon J. Freeman, Arnold S. Freedman, Lee M. Nadler
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Publication number: 20030170821Abstract: Isolated nucleic acid molecules encoding a B cell activation antigen, B7, are provided. In one embodiment, the nucleic acid molecules are DNA sequences. The DNA sequences of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also provided are host cells transformed to produce proteins or peptides encoded by the DNA molecules of the present invention and purified proteins and peptides which comprise at least a portion of the B cell activation antigen. The proteins and peptides comprise at least a portion of the mature form of the B7 activation antigen and preferably comprise a soluble form of the B7 protein.Type: ApplicationFiled: April 19, 2002Publication date: September 11, 2003Applicant: The Dana-Farber Cancer InstituteInventors: Gordon J. Freeman, Arnold S. Freedman, Lee M. Nadler
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Publication number: 20030158402Abstract: Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferationare disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.Type: ApplicationFiled: December 16, 2002Publication date: August 21, 2003Applicant: Dana-Farber Cancer InstituteInventors: Kathryn T. Hall, Gordon J. Freeman, Joachim L. Schultze, Vassiliki A. Boussiotis, Lee M. Nadler