Gordon L Freeman

US Patent:

6451305, Sep 17, 2002

Filed:

Jun 1, 1995

Appl. No.:

08/457483

Inventors:

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

Assignee:

Dana-Farber Cancer Institute

International Classification:

A61K 4800

US Classification:

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

Abstract:

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.

US Patent:

6465251, Oct 15, 2002

Filed:

Nov 13, 1996

Appl. No.:

08/748341

Inventors:

Joachim L. Schultze - Brookline MA
Gordon J. Freeman - Brookline MA
John G. Gribben - Brookline MA
Lee M. Nadler - Newton MA

Assignee:

Dana-Farber Cancer Institute, Inc. - Boston MA

International Classification:

C12N 502

US Classification:

435377, 435 2, 435325, 435326, 435352, 435355, 435363, 435366, 435372, 4353721, 4353722, 435374, 435375, 435376, 435383

Abstract:

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 1Ã10 to 1Ã10 fold in 2 weeks or 1Ã10 to 1Ã10 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.

US Patent:

6576754, Jun 10, 2003

Filed:

Nov 9, 1995

Appl. No.:

08/556422

Inventors:

Kathryn T. Hall - Boston MA
Gordon J. Freeman - Brookline MA
Joachim L. Schultze - Pulheim, DE
Vassiliki A. Boussiotis - Brookline MA
Lee M. Nadler - Newton MA

Assignee:

Dana-Farber Cancer Institute - Boston MA

International Classification:

C07H 2104

US Classification:

536 235, 536 231

Abstract:

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.

US Patent:

6605279, Aug 12, 2003

Filed:

Oct 22, 1999

Appl. No.:

09/425762

Inventors:

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

Assignee:

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

International Classification:

A61K 39395

US Classification:

4241531, 4241301, 4241391, 4241411, 4241431, 4241441, 4241731, 5303871, 5303881, 5303873, 5303882, 53038822, 5303887, 53038873, 435326, 435331, 435332, 435334, 435343, 4353431, 435346

Abstract:

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.

US Patent:

6608180, Aug 19, 2003

Filed:

Apr 17, 2001

Appl. No.:

09/837867

Inventors:

Arlene H. Sharpe - Brookline MA
Francescopaolo Borriello - Brookline MA
Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA

Assignee:

Brigham Womens Hospital - Boston MA
Dana-Farber Cancer Institute - Boston MA

International Classification:

C07K 1628

US Classification:

5303879, 5303871, 5303882, 53038822, 5303887, 53038873, 530350

Abstract:

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.

US Patent:

6653444, Nov 25, 2003

Filed:

May 30, 1995

Appl. No.:

08/453386

Inventors:

Gordon J. Freeman - Brookline MA
Arnold S. Freedman - Newton MA
Lee M. Nadler - Newton MA

Assignee:

Dana-Farber Cancer Institute, Inc. - Boston MA

International Classification:

C07K 14705

US Classification:

530350, 4241841, 4241851, 4241921, 514 2, 514 8, 514885, 536 231, 536 234, 536 235

Abstract:

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.

US Patent:

6719972, Apr 13, 2004

Filed:

Jun 3, 1994

Appl. No.:

08/253783

Inventors:

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

Assignee:

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

International Classification:

A61K 39395

US Classification:

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

Abstract:

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.

US Patent:

6723705, Apr 20, 2004

Filed:

Dec 7, 1998

Appl. No.:

09/206132

Inventors:

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

Assignee:

Gentics Institute, Inc. - Cambridge MA

International Classification:

A61K 3170

US Classification:

514 44, 435455, 4353201, 536 235, 536 245

Abstract:

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. A method for specifically inducing a CD4 T cell response against a tumor and a method for treating a tumor by modification of tumor cells in vivo are disclosed.