Compositions and methods for eliminating undesired subpopulations of T cells in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation
AssigneeXCYTE Therapies, Inc.
InventorsRonald Berenson, Mark Bonyhadi, Dale Kalamasz
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Abstract
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.
Claims67
A method for eliminating at least a substantial portion of a clonal T cell subpopulation from a mixed population of T cells from an individual, comprising,
- exposing a population of cells, wherein at least a portion thereof comprises T cells, to one or more pro-apoptotic or growth inhibiting compositions wherein said exposure induces apoptosis or growth inhibition in at least a substantial portion of at least one clonal T cell population present in the mixed population of T cells;
- thereby eliminating at least a substantial portion of said clonal T cell population from the mixed population of T cells.
A method for eliminating at least a substantial portion of a clonal T cell subpopulation from a mixed population of T cells from an individual, comprising,
- (a) exposing a population of cells wherein at least a portion thereof comprises T cells to one or more compositions that sensitize at least a portion of the T cells to further activation or stimulation,
- (b) exposing the population of cells to a surface wherein the surface has attached thereto one or more agents that ligate a cell surface moiety of at least a portion of the sensitized T cells and stimulates said sensitized T cells, wherein the exposure of said sensitized T cells to said surface is for a time sufficient to induce apoptosis of said sensitized T cells;
- thereby eliminating said sensitized T cells from the population.
A method for generating a substantially pure population of CD3+/CD28+ T cells from a population of T cells from an individual, comprising:
- exposing a population of cells, wherein at least a portion thereof comprises T cells, ex vivo to a composition that stimulates and/or selects surface CD3 and CD28 molecules;
- thereby generating a substantially pure population of CD3+/CD28+ T cells.
A method for generating a substantially pure population of CD4+/CD3+/CD28+ T cells from a population of T cells from an individual, comprising:
- exposing a population of cells, wherein at least a portion thereof comprises T cells, ex vivo to a composition that stimulates and/or selects surface CD3 and CD28 molecules;
- thereby generating a substantially pure population of CD4+/CD3+/CD28+ T cells.
A method for generating a substantially pure population of CD8+/CD3+/CD28+ T cells from a population of T cells from an individual, comprising:
- exposing a population of cells, wherein at least a portion thereof comprises T cells, ex vivo to a composition that stimulates and/or selects surface CD3 and CD28 molecules;
- thereby generating a substantially pure population of CD8+/CD3+/CD28+ T cells.
A method for activating and expanding a population of T cells by cell surface moiety ligation, comprising:
- contacting a population of cells, wherein at least a portion thereof comprises T cells, with a surface, wherein said surface has attached thereto one or more agents that ligate a cell surface moiety of at least a portion of the T cells and stimulates said T cells, wherein said surface is present at a ratio of said surface to said cells such that at least a substantial portion of at least one population of antigen-specific T cells is deleted after about 8 days of culture.
Dependencies are inferred from the claim text.