Methods of manufacturing t cell therapies
AssigneeCelgene Corporation
InventorsDavid R. MERTZ, Jaymes FULLER, Erica GRAF, Jessica MARFO
Life of this patent
Estimating the term…
Abstract
The present disclosure provides cell populations enriched for CD28 positive T cells, and methods for stimulating, genetically engineering, and/or cultivating such cell populations. Also included are methods for generating, isolating, enriching, or selecting CD28 positive T cells or populations of cells enriched for CD28 positive T cells.
Claims146
A method of selecting cells for manufacture of a cell therapy, comprising:
- (1) determining the percentage of CD28+ T cells in a first biological sample obtained from a subject, wherein the first biological sample comprises T cells;
- and
- (2) selecting the subject for manufacturing a cell therapy from a second biological sample obtained from the subject if the percentage of CD28+ T cells in the first biological sample is above a threshold value, wherein the second biological sample comprises T cells.
A method of manufacturing a cell therapy, comprising:
- (1) selecting a subject for manufacturing a cell therapy if the percentage of CD28+ T cells in a first biological sample obtained from the subject is above a threshold value, wherein the first biological sample comprises T cells;
- and
- (2) genetically engineering cells of a second biological sample obtained from the subject to express a recombinant receptor, thereby generating a cell therapy comprising the genetically engineered cells, wherein the second biological sample comprises T cells.
A method of treating a subject with a cell therapy, comprising administering a dose of a cell therapy comprising genetically engineered cells to a subject, wherein:
- (1) the percentage of CD28+ T cells in a first biological sample obtained from a subject is determined to be above a threshold value, wherein the first biological sample comprises T cells;
- (2) the subject is selected for manufacture of the cell therapy based on the determining in step (1);
- and
- (3) cells of a second biological sample obtained from the subject are genetically engineered to express a recombinant receptor, thereby generating the cell therapy, wherein the second biological sample comprises T cells.
A method of selecting cells for manufacture of a cell therapy, comprising:
- (1) determining the percentage of CD28+ T cells in a first biological sample obtained from a subject;
- and
- (2) selecting the subject for manufacturing a cell therapy from a second biological sample obtained from the subject if the percentage of CD28+ T cells in the first biological sample is above a threshold value,
- wherein the first biological sample and the second biological sample are the same sample, which is an apheresis sample.
A method of manufacturing a cell therapy, comprising:
- (1) selecting a subject for manufacturing a cell therapy if the percentage of CD28+ T cells in a first biological sample obtained from the subject is above a threshold value;
- and
- (2) genetically engineering cells of a second biological sample obtained from the subject to express a recombinant receptor, thereby generating a cell therapy comprising the genetically engineered cells,
- wherein the first biological sample and the second biological sample are the same sample, which is an apheresis sample.
A method of treating a subject with a cell therapy, comprising administering a dose of a cell therapy comprising genetically engineered cells to a subject, wherein:
- (1) the percentage of CD28+ T cells in a first biological sample obtained from a subject is determined to be above a threshold value;
- (2) the subject is selected for manufacture of the cell therapy based on the determining in step (1);
- and
- (3) cells of a second biological sample obtained from the subject are engineered to express a recombinant receptor, thereby generating the cell therapy,
- wherein the first biological sample and the second biological sample are the same sample, which is an apheresis sample.
A method of enriching for CD28+ cells, the method comprising:
- (a) performing a first selection, the first selection comprising enriching for either of CD28+ or CD3+ cells from a biological sample comprising peripheral blood mononuclear cells (PBMCs) obtained from a subject, thereby generating an enriched cell population;
- and
- (b) performing a second selection on the cells of the enriched cell population, thereby generating a CD28+ enriched population, wherein (i) the first selection comprises enriching for CD28+ cells and the second selection comprises enriching for CD3+ cells from the enriched population;
- or (ii) the first selection comprises enriching for CD3+ cells and the second selection comprises enriching for CD28+ cells from the enriched cell population,
- wherein the CD28+ enriched population has a higher percentage of CD28+ cells than the biological sample and is enriched for CD3+ cells.
A method of enriching for CD28+ cells, the method comprising:
- (a) performing a first selection, the first selection comprising enriching for CD28+ cells from a biological sample comprising peripheral blood mononuclear cells (PBMCs) obtained from a subject, thereby generating a first enriched population, the first enriched population having a higher percentage of CD28+ cells than the biological sample;
- (b) performing a second selection on the cells from the first enriched population, the second selection comprising enriching for one of (i) CD4+ cells and (ii) CD8+ cells from the first enriched population, the enrichment thereby generating a second enriched population enriched for the one of (i) CD4+ cells and (ii) CD8+ cells and a non-selected population;
- and
- (c) performing a third selection, the third selection comprising enriching for the other of (i) CD4+ cells and (ii) CD8+ cells from the non-selected population, the enrichment thereby generating a third enriched population enriched for the other of the (i) CD4+ cells and (ii) CD8+ cells.
A method of treating a disease or condition in a human subject with a T cell therapy, the method comprising administering to a human subject having a disease or condition a therapeutically effective amount of a T cell therapy, wherein:
- (a) at least about 40% of T cells in the subject are CD28+;
- and
- (b) manufacture of the T cell therapy relies on CD28-mediated expansion of the T cells of the T cell therapy.
A method of treating multiple myeloma in a human subject, the method comprising administering to a human subject having a multiple myeloma a therapeutically effective amount of a T cell therapy, wherein at least about 40% of T cells in the subject are CD28+.
A method of increasing proliferation of T cells comprising incubating a population of T cells under stimulating conditions, wherein the population of T cells comprises a percentage of CD28+ T cells above a threshold value.
A method of increasing proliferation of T cells comprising:
- (1) selecting a biological sample comprising a population of T cells in which the percentage of CD28+ T cells in the population of T cells is above a threshold value;
- and
- (2) incubating the selected population of T cells under stimulating conditions.
A method of manufacturing a cell therapy, comprising:
- (1) selecting a subject for manufacturing a cell therapy if the percentage of any of CD28+, CD45RA+, CD45RO+, CD27+, CD197+, CD4+, CD57+, CD8+, CD25+, PD1+, LAG3+, CD3+ and/or TIM3+ T cells in a first biological sample obtained from the subject is above a threshold value, wherein the first biological sample comprises T cells;
- and
- (2) genetically engineering cells of a second biological sample obtained from the subject to express a recombinant receptor, thereby generating a cell therapy comprising the genetically engineered cells, wherein the second biological sample comprises T cells.
Dependencies are inferred from the claim text.