LEE MARSHALL NADLER, M.D.
Osteopathic Medicine in Boston, MA

6824779, Nov 30, 2004

Oct 22, 1999

09/425516

Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA
Gary S. Gray - Brookline MA

Dana-Farber Cancer Institute, Inc. - Boston MA
Genetics Institute, LLC - Cambridge MA

A61K 39395

4241531, 4241301, 4241331, 4241411, 4241431, 4241441, 4241731, 5303871, 5303873, 5303881, 5303882, 53038822, 5303887, 53038873

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.

6451305, Sep 17, 2002

Jun 1, 1995

08/457483

Vassiliki A. Boussiotis - Brookline MA
Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA

Dana-Farber Cancer Institute

A61K 4800

424 9321, 424 932, 424 937, 435325, 4353651, 435440, 435455

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.

6719972, Apr 13, 2004

Jun 3, 1994

08/253783

John G. Gribben - Brookline MA
Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA
Paul Rennert - Holliston MA
Cindy L. Jellis - Londonderry NH
Edward Greenfield - Randolph MA
Gary S. Gray - Brookline MA

Repligen Corporation - Cambridge MA
Dana-Farber Cancer Institute - Boston MA

A61K 39395

4241541, 4241301, 4241331, 4241341, 4241391, 4241411, 4241431, 4241441, 4241451, 4241531, 4241731, 5303871, 5303873, 5303879, 5303881, 5303882, 53038822, 5303887, 53038873, 53038875

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. Methods for inducing T cell apoptosis in vitro with an anti-CTLA4 antibody or other ligand of the invention together with an antigen specific signal are also disclosed, e. g.

2004003, Feb 26, 2004

Jun 10, 2003

10/458069

Vassiliki Boussiotis - Brookline MA, US
Lee Nadler - Newton MA, US

Dana-Farber Cancer Institute - Boston MA

A61K038/20, A61K039/395

424/085200, 424/144100

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 chain (e.g., interleukin-2 receptor, interleukin-4 receptor, interleukin-7 receptor) prevents the induction of T cell anergy. This 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 chain induces phosphorylation of the JAK kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor chain are disclosed.

6084067, Jul 4, 2000

Jun 7, 1995

8/479744

Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA
Gary S. Gray - Brookline MA

Dana-Farber Cancer Institute - Boston MA
Genetics Institute, Inc. - Cambridge MA

C07K 1447

530350

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.

7851591, Dec 14, 2010

Oct 29, 1999

09/830400

Lee M. Nadler - Newton MA, US
William C. Hahn - Waltham MA, US
Joachim L. Schultze - Brookline MA, US
Robert H. Vonderheide - Brookline MA, US

Dana Farber Cancer Institute, Inc. - Boston MA

C07K 5/00, C07K 7/00, C07K 16/00, C07K 17/00, A61K 38/04

530328

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.

2003017, Sep 11, 2003

Apr 19, 2002

10/126088

Gordon Freeman - Brookline MA, US
Arnold Freedman - Newton MA, US
Lee Nadler - Newton MA, US

The Dana-Farber Cancer Institute

C12P021/02, C12N005/06, C07K014/705, C07H021/04

435/069300, 435/320100, 435/325000, 530/350000, 536/023200

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.

6149905, Nov 21, 2000

Sep 23, 1998

9/159135

Sivasubramanian Baskar - Ellicott City MD
Laurie H. Glimcher - West Newton MA
Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA

Genetics Institute, Inc. - Cambridge MA
Dana-Farber Cancer Institute - Boston MA
Presidents and Fellows of Harvard College - Cambridge MA

A61K 4800

424 9321

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. + T cell response against a tumor and a method for treating a tumor by modification of tumor cells in vivo are disclosed.

7955845, Jun 7, 2011

May 20, 2004

10/850294

Naoto Hirano - Brookline MA, US
Marcus Butler - Jamaica Plain MA, US
Lee M. Nadler - Newton MA, US

Dana Farber Cancer Institute, Inc. - Boston MA

C12N 5/071, C12N 5/00, C12N 5/02, C12N 15/00

435325, 435455, 435366

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.

5942607, Aug 24, 1999

Jul 26, 1993

8/101624

Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA
Gary S. Gray - Brookline MA

Dana-Farber Cancer Institute - Boston MA

C07H 2100, C07K 14705, C12N 1512

536 235

Isolated nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the isolated nucleic acid has a sequence which encodes a B lymphocyte activation 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. The nucleic acid 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 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.