Methods for selectively stimulating proliferation of T cells
First Claim
1. A method for expanding a population of CD8+ T cells in number of from about 100 to about 100,000 fold over the original CD8+ T cell population or to about 10 log10 to 12 log10, comprising;
- a) contacting a population of CD8+ T cells with a surface comprising1) an anti-CD3 antibody or a CD-3-binding fragment thereof; and
2) a second agent which stimulates a CD28 antigen, wherein the second agent is selected from the group consisting of an anti-CD28 antibody or a CD28-binding fragment thereof, B7-1 or a CD28-binding fragment thereof, B7-2 or a CD28-binding fragment thereof, a B7-1Ig fusion protein that interacts with CD28 and a B7-2Ig fusion protein that interacts with CD28, wherein said anti-CD3 antibody or CD3-binding fragment thereof, and said second agent are attached on the same surface;
b) adding exogenous IL-2 to the population of CD8+ T cells, such that the population of CD8+ T cells increase in number from about 100 to about 100,000 fold over the original CD8+ T cell population or to about 10 log10 to 12 log10.
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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.
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Citations
24 Claims
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1. A method for expanding a population of CD8+ T cells in number of from about 100 to about 100,000 fold over the original CD8+ T cell population or to about 10 log10 to 12 log10, comprising;
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a) contacting a population of CD8+ T cells with a surface comprising 1) an anti-CD3 antibody or a CD-3-binding fragment thereof; and 2) a second agent which stimulates a CD28 antigen, wherein the second agent is selected from the group consisting of an anti-CD28 antibody or a CD28-binding fragment thereof, B7-1 or a CD28-binding fragment thereof, B7-2 or a CD28-binding fragment thereof, a B7-1Ig fusion protein that interacts with CD28 and a B7-2Ig fusion protein that interacts with CD28, wherein said anti-CD3 antibody or CD3-binding fragment thereof, and said second agent are attached on the same surface; b) adding exogenous IL-2 to the population of CD8+ T cells, such that the population of CD8+ T cells increase in number from about 100 to about 100,000 fold over the original CD8+ T cell population or to about 10 log10 to 12 log10. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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Specification