Th1 cell adoptive immunotherapy
OwnerMicheal L. Gruenberg, Surenda Chavaninventors
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Abstract
Methods for consistently producing a pure population of activated, polyclonal, Th1 memory cells for use in adoptive immunotherapy without the use of any exogenous cytokines and without significant subject-to-subject variation are provided. The resulting cells obtain a surface phenotype that enables their trafficking to tumors and other sites of inflammation upon infusion. The cells can be reinfused into the a subject to enhance the cellular immune response and/or switch the predominant immune response from Th2-dominated to a Th1-dominated immune response.
Claims86
A method for producing a highly pure population of Th1 cells, comprising:
- purifying T-cells from the source material;
- and
- activating the T-cells a plurality of times, whereby a highly pure population of Th1 cells is produced.
A method comprising:
- (a) collecting a sample of mononuclear cells from a subject with a disease characterized by either an excess of Th2 cytokine activity or low Th1 cytokine activity;
- and
- (b) processing the mononuclear cells ex vivo without the use of any exogenous cytokines to produce an expanded population of highly pure Th1 memory cells.
A composition, comprising at least about 90% activated Th1 cells.
A process for producing compositions comprising at least 70% Th1 cells, comprising:
- (a) collecting a sample of mononuclear cells from a subject with a disease characterized by either an excess of Th2 cytokine activity or lack of Th1 cytokine activity;
- (b) removing platelets from the sample;
- (c) removing macrophages from the sample;
- (c) depleting CD45RO+ cells from the sample by negative selection;
- (d) selecting the CD4+ cells by positive selection;
- and
- (e) expanding and differentiating the selected CD4+ cells by repeatedly stimulating the selected CD4+ cells with immobilized anti-CD3/anti-CD28 antibodies.
A process for producing compositions that have an enhanced population of activated polyclonal Th1 memory cells, comprising:
- (a) collecting a sample of mononuclear cells from a subject;
- (b) expanding and differentiating the mononuclear cells by repeatedly activating T-cells in the mononuclear cell sample in the absence of exogenous growth or differentiation factors, thereby producing a highly pure population of activated polyclonal Th1 memory cells.
A method for expanding T-cells from cancer patients without the use of exogenous cytokines, comprising:
- (a) collecting a mononuclear cell sample from a cancer patient;
- (b) purging platelets from the mononuclear cells;
- and
- (c) activating the cells with immobilized anti-CD3/anti-CD28 mAbs, wherein all steps are performed in the absence of exogenous cytokines.
A composition of cells, comprising at least about 109 cells, wherein at least about 70% of the cells are polyclonal Th1 memory cells.
A highly pure population of Th1 cells, wherein at least 70% are positive for internal interferon-γ and the cells are at a density of at least 1010 cells/liter.
A composition, comprising at least 70% polyclonal memory Th1 cells.
Dependencies are inferred from the claim text.