Methods for eliminating at least a substantial portion of a clonal antigen-specific memory T cell subpopulation
View Patent ↗The present invention relates generally to methods for stimulating T cells, and more particularly, to methods to eliminate undesired (e.g., autoreactive, alloreactive, pathogenic) subpopulations of T cells from a mixed population of T cells, thereby restoring the normal immune repertoire of said T cells. The present invention also relates to compositions of cells, including stimulated T cells having restored immune repertoire and uses thereof.
1. A method for activating and expanding naïve T cells present in a mixed population of T cells comprising naïve T cells and antigen-specific memory T cells, the method comprising:
contacting the mixed population of T cells with a surface having attached thereto agents with binding activity to cell surface moieties on the surfaces of T cells in the mixed population,
thereby (a) expanding naïve T cells, and (b) deleting antigen-specific memory T cells present in the mixed population of T cells,
wherein the agents having binding affinity for CD3 protein complexes and CD28 proteins, and
wherein the ratio of surface to cells is at least 5:1.
2. The method of claim 1 , wherein one or both of the agents are antibodies or an antibody fragments.
3. The method of claim 1 , wherein one of the agents is an anti-CD3 antibody or an anti-CD3 antibody fragment.
4. The method of claim 1 , wherein one of the agents is an anti-CD28 antibody or an anti-CD28 antibody fragment.
5. The method of claim 1 , wherein an anti-CD3 antibody or an anti-CD3 antibody fragment and an anti-CD28 antibody or an anti-CD28 antibody fragment are co-localized on the same surface.
6. The method of claim 1 , wherein the ratio of surface to cells is between 5:1 and 10:1.