US 6,887,466 B2Granted

Methods for selectively stimulating proliferation of T cells

AssigneesGenetics Institute, Inc., The Regents of the University of Michigan, The United States of America as represented by the Secretary of the Navy

InventorsCarl H. June, Craig B. Thompson, Gary J. Nabel, Gary S. Gray, Paul D. Rennert

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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.

Claims19

Dependent claims

A method for inducing ex vivo proliferation of a population of T cells to sufficient numbers for use in therapy, comprising contacting a population of T cells ex vivo with a surface having covalently attached thereto:

(a) an anti-CD3 antibody or CD3-binding fragment thereof, which provides a primary activation signal to the T cells, thereby activating the T cells;
and
(b) an anti-CD28 antibody or CD28-binding fragment thereof, which stimulates a CD28 accessory molecule on the surface of the T cells, thereby stimulating the activated T cells,
wherein the anti-CD3 antibody or CD3-binding fragment thereof, and the anti-CD28 antibody or CD28-binding fragment thereof, are covalently attached to the same surface,
the anti-CD3 antibody or CD3-binding fragment thereof, and the anti-CD28 antibody or CD28-binding fragment thereof, thereby inducing the population of T cells to proliferate to sufficient numbers for use in therapy.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/350,202Filed 8 Jul 1999 · continuation
Priority: 3 Jun 1994
Published: US 2003/0099643 A129 May 2003
Granted: 3 May 2005
Term ends: Not estimatedThe source records don’t support an estimate.

Classification37 codes

C12N 5/0636
Cells from the blood or the immune system: t lymphocytes
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/421
Receptors, cell surface antigens or cell surface determinants: immunoglobulin superfamily
A61K 40/46
Characterised by antigens that are targeted or presented by cells of the immune system: viral antigens

Family

Application08/253,964Parent of this continuation-in-part · filed 3 Jun 1994
Application08/403,253Parent of this continuation · filed 10 Mar 1995
US 2003/0099643 A1Pre-grant publication · published 29 May 2003
US 6,352,694 B1Parent of this continuation
US 5,635,697 AParent of this continuation-in-part
Application08/403,253Parent of this continuation-in-part
US 6,887,466 B2This patent

From the US filing history. Foreign family members aren’t listed.