Methods for selectively stimulating proliferation of T cells

An ex vivo method for inducing a population of CD4+ T cells to proliferate to sufficient numbers for use in therapy, comprising:

• (a) activating a population of CD4+ T cells with an agent which stimulates a TCR/CD3 complex-associated signal in the CD4+ T cells, wherein the agent is selected from the group consisting of an anti-CD3 antibody or a CD3-binding fragment thereof, an anti-CD2 antibody or a CD2-binding fragment thereof, and an antigen in a form suitable to trigger a primary activation signal in the T cell when complexed with the TCR/CD3 complex, wherein the agent is attached on a surface;
• and
• (b) stimulating a CD28 accessory molecule on the surface of the T cells with a ligand that binds the CD28 accessory molecule on the surface of the T cells, wherein the ligand 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, and B7-2 or a CD28-binding fragment thereof, wherein the ligand is attached on the same surface as said agent,
• the activating and stimulating steps thereby inducing proliferation of the CD4+ T cells to sufficient numbers for use in therapy, and resulting in a population of CD4+ T cells that are polyclonal with respect to antigen reactivity.

A method for expanding a population of T cells to sufficient numbers for use in therapy, comprising:

• a) activating the population of T cells by contacting the T cells in vitro with an anti-CD3 antibody or a CD3-binding fragment thereof, which is attached on a surface;
• and
• b) stimulating a CD28 accessory molecule on the surface of the T cells in vitro with an anti-CD28 antibody or a CD28-binding fragment thereof, wherein said anti-CD28 antibody or CD28-binding fragment thereof is attached on the same surface as the anti-CD3 antibody or CD3-binding fragment thereof,
• the activating and stimulating steps thereby expanding the population of the T cells to sufficient numbers for use in therapy.

A method for producing a population of T cells suitable for augmenting or supporting T cell growth in vivo, comprising:

• a) activating the population of T cells by contacting the T cells in vitro with an anti-CD3 antibody or a CD3-binding fragment thereof, which is attached on a surface;
• and
• b) stimulating a CD28 accessory molecule on the surface of the T cells in vitro with an anti-CD28 antibody or a CD28-binding fragment thereof, wherein said anti-CD28 antibody or CD28-binding fragment thereof is attached on the same surface as the anti-CD3 antibody or CD3-binding fragment thereof,
• the activating and stimulating steps thereby producing a population of T cells suitable for augmenting or supporting T cell growth in vivo.