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).
-
Patent number: 6608180Abstract: 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: April 17, 2001Date of Patent: August 19, 2003Assignees: Brigham & Womens' Hospital, Dana-Farber Cancer InstituteInventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
-
Therapeutic compositions for inhibiting the interactions of B7-1 and B7-2 with their natural ligands
Patent number: 6605279Abstract: Disclosed is a composition for inhibiting the interactions of B7-1 and B7-2 with their natural ligands. Such compositions comprise an antibody specific for B7-2 and an antibody specific for B7-1, in a pharmaceutically acceptable carrier. The composition may be formulated for either separate or combined administration of the antibody components. The antibodies may be monoclonal antibodies, or humanized antibodies. Preferred antibodies are disclosed.Type: GrantFiled: October 22, 1999Date of Patent: August 12, 2003Assignees: Genetics Institute, Inc., Dana-Farber Cancer InstituteInventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray -
Publication number: 20030124103Abstract: 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: ApplicationFiled: September 30, 2002Publication date: July 3, 2003Inventors: Suzanne Ostrand-Rosenberg, Sivasubramanian Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
-
Patent number: 6576236Abstract: 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: GrantFiled: July 1, 1994Date of Patent: June 10, 2003Assignee: Dana Farber Cancer InstituteInventors: Vassiliki A. Boussiotis, Lee M. Nadler
-
Patent number: 6576754Abstract: 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: November 9, 1995Date of Patent: June 10, 2003Assignee: Dana-Farber Cancer InstituteInventors: Kathryn T. Hall, Gordon J. Freeman, Joachim L. Schultze, Vassiliki A. Boussiotis, Lee M. Nadler
-
Publication number: 20030045703Abstract: 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: September 24, 2001Publication date: March 6, 2003Applicant: Bright and Women's HospitalInventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
-
Publication number: 20030044416Abstract: 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: November 9, 1995Publication date: March 6, 2003Applicant: DANA-FARBER CANCER INSTITUTEInventors: KATHRYN T. HALL, GORDON J. FREEMAN, JOACHIM L. SCHULTZE, VASSILIKI A. BOUSSIOTIS, LEE M. NADLER
-
Methods for selectively modulating a Th2-type response within a population of activated CD4+ T cells
Publication number: 20020182727Abstract: Methods for selectively modulating a Th2-type response within a population of activated CD4+ T cells are provided. The methods of the invention involve contacting the CD4+ T cells with an agent which modulates a B7-2-induced signal in the CD4+T cells, such that the Th2-type response is modulated. Methods for either stimulating or inhibiting Th2 type responses are provided by the invention.Type: ApplicationFiled: March 11, 2002Publication date: December 5, 2002Applicant: Dana-Farber Cancer InstituteInventors: Gordon J. Freeman, Vassiliki A. Boussiotis, Lee M. Nadler -
Patent number: 6465251Abstract: 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&bgr;.Type: GrantFiled: November 13, 1996Date of Patent: October 15, 2002Assignee: Dana-Farber Cancer Institute, Inc.Inventors: Joachim L. Schultze, Gordon J. Freeman, John G. Gribben, Lee M. Nadler
-
Patent number: 6451305Abstract: Methods for stimulating a T cell response to a tumor cell in a subject with a tumor which involve modifying the tumor cell to express a CD2 ligand and a CD28 or CTLA4 ligand, are disclosed. Methods wherein the tumor cell is obtained from the subject and modified ex vivo to form a modified tumor cell and then the modified tumor cell is administered to the subject, are also disclosed.Type: GrantFiled: June 1, 1995Date of Patent: September 17, 2002Assignee: Dana-Farber Cancer InstituteInventors: Vassiliki A. Boussiotis, Gordon J. Freeman, Lee M. Nadler
-
Publication number: 20020127201Abstract: 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, interleukin-15 receptor) prevents the induction of T cell anergy. This &ggr; chain has been found to be associated with a JAK3 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 JAK3 kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor &ggr; chain are disclosed.Type: ApplicationFiled: May 7, 2002Publication date: September 12, 2002Applicant: Dana-Farber Cancer Institute.Inventors: Vassiliki A. Boussiotis, Lee M. Nadler
-
Publication number: 20020098542Abstract: 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: April 19, 2001Publication date: July 25, 2002Applicant: Brigham and Womens' HospitalInventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
-
Publication number: 20020086414Abstract: 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: October 22, 1999Publication date: July 4, 2002Inventors: GORDON J. FREEMAN, LEE M. NADLER, GARY S. GRAY
-
Publication number: 20020086421Abstract: TUMOR CELLS WITH INCREASED IMMUNOGENICITY AND USES THEREFOR 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: ApplicationFiled: September 27, 2001Publication date: July 4, 2002Applicant: University of MarylandInventors: Suzanne Ostrand-Rosenberg, Sivasubramanian Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
-
Publication number: 20020051784Abstract: Methods for modulating antigen-specific T cell unresponsiveness which involve inhibiting or stimulating an unresponsive T cell through a cell surface receptor, CD2, are disclosed. Agents which inhibit stimulation of an unresponsive T cell through a CD2 surface receptor are useful therapeutically in situations where it is desirable to inhibit an immune response to an antigen(s), for example in organ or bone marrow transplantation and autoimmune diseases. Methods for reversing T cell unresponsiveness by contacting the T cell with an agent which stimulates the T cell through a CD2 surface receptor are useful therapeutically to stimulate an immune response to an antigen(s). For example, the method is useful to stimulate an anti-tumor response in a subject with a tumor or stimulate a response against a pathogenic agent or increase the efficacy of vaccination.Type: ApplicationFiled: November 28, 2001Publication date: May 2, 2002Applicant: Dana Farber Cancer instituteInventors: Vassiliki A. Boussiotis, Gordon J. Freeman, Lee M. Nadler
-
Patent number: 6319709Abstract: 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: November 29, 1999Date of Patent: November 20, 2001Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, University of Maryland, Baltimore CountyInventors: Suzanne Ostrand-Rosenberg, Sivasubramanian Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
-
Patent number: 6294660Abstract: Nucleic acids encoding B7-1 and B7-2 molecules which bind CD28 or CTLA4 are described. These structural forms correspond to naturally-occurring alternatively spliced forms comprising cytoplasmic and signal peptide domains of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. These T cell costimulatory molecules can be used to identify agents which stimulate the express of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.Type: GrantFiled: February 7, 1997Date of Patent: September 25, 2001Assignees: Dana-Farber Cancer Institute Brigham, Women's HospitalInventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
-
Patent number: 6218510Abstract: Structural forms of T cell costimulatory B7-1 and B7-2 molecules are described. These structural forms comprise a 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 cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a signal peptide domain or has an immunoglobulin variable region-like domain deleted. The 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: March 2, 1994Date of Patent: April 17, 2001Assignees: Brigham & Woman's Hospital, Dana-Farber Cancer InstituteInventors: Arlene H. Sharpe, Francescopaolo Borriello, Gordon J. Freeman, Lee M. Nadler
-
Patent number: 6149905Abstract: 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. A method for specifically inducing a CD4.sup.Type: GrantFiled: September 23, 1998Date of Patent: November 21, 2000Assignees: Genetics Institute, Inc., Dana-Farber Cancer Institute, Presidents and Fellows of Harvard CollegeInventors: Suzanne Ostrand-Rosenberg, Sivasubramanian Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
-
Patent number: 6130316Abstract: 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: July 26, 1994Date of Patent: October 10, 2000Assignees: Dana Farber Cancer Institute, Replingen CorporationInventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray, Edward Greenfield