Carl Howard June

US Patent:

6352694, Mar 5, 2002

Filed:

Mar 10, 1995

Appl. No.:

08/403253

Inventors:

Carl H. June - Rockville MD
Craig B. Thompson - Chicago IL
Gary J. Nabel - Ann Arbor MI
Gary S. Gray - Brookline MA
Paul D. Rennert - Holliston MA

Assignee:

Genetics Institute, Inc. - Cambridge MA
The Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K 3514

US Classification:

424 9371, 424 937, 424534, 424577, 424578, 435 2, 435375, 435377

Abstract:

Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

US Patent:

6534055, Mar 18, 2003

Filed:

May 4, 1995

Appl. No.:

08/435816

Inventors:

Carl H. June - Rockville MD
Craig B. Thompson - Chicago IL
Gary J. Nabel - Ann Arbor MI
Gary S. Gray - Brookline MA
Paul D. Rennert - Holliston MA

Assignee:

Genetics Institute, Inc. - Cambridge MA

International Classification:

A61K 3514

US Classification:

424 9371, 424 937, 424534, 424577, 424578, 435 2, 435375, 435377

Abstract:

Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

US Patent:

6632789, Oct 14, 2003

Filed:

Apr 29, 1994

Appl. No.:

08/245282

Inventors:

Carl H. June - Rockville MD

Assignee:

The United States of America as represented by the Secretary of the Navy - Washington DC

International Classification:

A01N 6100

US Classification:

514 1, 514453, 4241301, 4242781

Abstract:

Methods for modulating T cell responses by manipulating intracellular signals associated with T cell costimulation are disclosed. The methods involve inhibiting or stimulating the production of at least one D3-phosphoinositide in a T cell. Production of D3-phosphoinositides can be manipulated by contacting a T cell with an inhibitor or activator of phosphatidylinositol 3-kinase. Inhibitors of phosphatidylinositol 3-kinase for use in the methods of the invention include wortmannin and quercetin, or derivatives or analogues thereof. The methods of the invention can further comprise modulating other intracellular signals associated with costimulation, such as protein tyrosine phosphorylation, for example by modulating the activity of a protein tyrosine kinase or a protein tyrosine phosphatase in the T cell. Inhibition of a T cell response in accordance with the disclosed methods is 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. Alternatively, stimulation of a T cell response in accordance with the disclosed methods is useful therapeutically to enhance an immune response to an antigen(s), for example to stimulate an anti-tumor response in a subject with a tumor, to stimulate a response against a pathogenic agent or increase the efficacy of vaccination.

US Patent:

6685941, Feb 3, 2004

Filed:

Feb 7, 1995

Appl. No.:

08/385194

Inventors:

Craig B. Thompson - Ann Arbor MI
Carl H. June - Rockville MD

Assignee:

The Regents of the University of Michigan - Ann Arbor MI
The United States of America as represented by the Secretary of the Navy - Washington DC

International Classification:

A61K 3817

US Classification:

4241341, 4241921, 514 2, 514 8, 514885, 530350, 5303873

Abstract:

The method of immunotherapy of the present invention involves the regulation of the T cell immune response through the activation or suppression/inactivation of the CD28 pathway. Induction of activated T cell lymphokine production occurs upon stimulatory binding of the CD28 surface receptor molecule, even in the presence of conventional immunosuppressants. Inhibition of CD28 receptor binding to an appropriate stimulatory ligand or inactivation of the CD28 signal transduction pathway through other means down-regulates CD28-pathway related T cell lymphokine production and its resulting effects.

US Patent:

6692964, Feb 17, 2004

Filed:

Jun 7, 1995

Appl. No.:

08/475136

Inventors:

Carl H. June - Rockville MD
Craig B. Thompson - Chicago IL
Suil Kim - Ann Arbor MI

Assignee:

The United States of America as represented by the Secretary of the Navy - Washington DC
The Regents of the University of Michigan - Ann Arbor MI

International Classification:

C12N 1563

US Classification:

435455, 4353201, 424 9321

Abstract:

A method for transfecting T cells with a nucleic acid molecule comprising a gene such that the gene is expressed in the T cells is described. The T cells are stimulated and proliferating prior to introduction of the nucleic acid molecule.

US Patent:

6887466, May 3, 2005

Filed:

Jul 8, 1999

Appl. No.:

09/350202

Inventors:

Carl H. June - Rockville MD, US
Craig B. Thompson - Chicago IL, US
Gary J. Nabel - Ann Arbor MI, US
Gary S. Gray - Brookline MA, US
Paul D. Rennert - Holliston MA, US

Assignee:

Genetics Institute, Inc. - Cambridge MA
Regents of the University of Michigan - Ann Arbor MI
The United States of America as represented by the Secretary of the Navy - Washington DC

International Classification:

A61K035/14
A61K035/26
A61K035/28

US Classification:

424 9371, 4241301, 4241411, 4241431, 4241441, 4241531, 4241541, 4241731, 424 937, 424534, 424577, 424578, 435 2, 435 71, 435 721, 435 724, 435375, 435377, 5303871, 5303881, 5303882, 53038822, 5303887, 53038873, 53038875

Abstract:

Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

US Patent:

6905680, Jun 14, 2005

Filed:

Jan 26, 1996

Appl. No.:

08/592711

Inventors:

Carl H. June - Rockville MD, US
Craig B. Thompson - Chicago IL, US
Gary J. Nabel - Ann Arbor MI, US
Gary S. Gray - Brookline MA, US
Paul D. Rennert - Holliston MA, US

Assignee:

Genetics Institute, Inc. - Cambridge MA
Regents of the University of Michigan - Ann Arbor MI
The United States of America as represented by the Secretary of the Navy - Washington DC

International Classification:

A61K035/14
A61K035/26
A61K035/28

US Classification:

424 9371, 4241301, 4241411, 4241431, 4241441, 4241531, 4241541, 4241731, 424 937, 424534, 424577, 424578, 435 2, 435 71, 435 721, 435 724, 435375, 435377, 5303871, 5303881, 5303882, 53038822, 5303887, 53038873, 53038875

Abstract:

Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

US Patent:

6905681, Jun 14, 2005

Filed:

Jul 8, 1999

Appl. No.:

09/349915

Inventors:

Carl H. June - Rockville MD, US
Craig B. Thompson - Chicago IL, US
Gary J. Nabel - Ann Arbor MI, US
Gary S. Gray - Brookline MA, US
Paul D. Rennert - Holliston MA, US

Assignee:

Genetics Institute, Inc. - Cambridge MA
Regents of the University of Michigan - Ann Arbor MI
The United States of America as represented by the Secretary of the Navy - Washington DC

International Classification:

A61K035/14
A61K035/26
A61K035/28

US Classification:

424 9371, 4241301, 4241411, 4241431, 4241441, 4241531, 4241541, 4241731, 424 937, 424534, 424577, 424578, 435 2, 435 71, 435 721, 435 724, 435375, 435377, 5303871, 5303881, 5303882, 53038822, 5303887, 53038873, 53038875

Abstract:

Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.