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US 2022/0177841 A1Published application
Ex vivo methods for producing a t cell therapeutic and related compositions and methods
AssigneeMyst Therapeutics, LLC
InventorsTimothy J. LANGER, Jacob CECCARELLI
Life of this patent
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Abstract
Provided herein are methods for ex vivo expansion of a T cells including tumor-reactive T cells, and compositions containing such T cells. Also provided are methods for treating diseases and conditions such as cancer using compositions of the present disclosure.
Claims156
A method for manufacturing tumor-reactive T cells, the method comprising:
- (1) culturing T cells by a process that comprises:
- (a) incubating a population of cells comprising T cells from a biological sample obtained from a subject that has a tumor with a first T cell stimulatory agent(s) under conditions to stimulate expansion of T cells of the population to produce a population of stimulated T cells;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (d) enriching from the co-culture the population of tumor reactive T cells reactive to the one or more peptides, wherein said tumor-reactive T cells comprise an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- and
- (d) incubating the population of T cells enriched in tumor reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of T cells in the population;
- and
- wherein one or more steps of the culturing is carried out in the presence of at least one T cell adjuvant that is an apoptosis inhibitor that inhibits caspase activation or activity;
- and
- (2) harvesting cells produced by the method to produce a composition of expanded T cells enriched in tumor reactive T cells.
7 more elements
A method for manufacturing tumor reactive T cells, the method comprising:
- (1) culturing T cells by a process comprising:
- (a) incubating a population of cells comprising T cells from a biological sample from a subject that has a tumor with a first T cell stimulatory agent(s) comprising one or more recombinant cytokines under conditions to stimulate expansion of T cells in the population to produce a population of stimulated T cells, wherein the incubation with the one or more recombinant cytokines is in the presence of at least one T cell adjuvant that is an apoptosis inhibitor that inhibits caspase activation or activity;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (c) enriching tumor-reactive T cells from the co-culture, said tumor-reactive T cells comprising an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- (d) incubating the population of T cells enriched for tumor-reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of cells of cells of the population of cells;
- and
- (2) harvesting cells produced by the method.
4 more elements
A method for manufacturing tumor-reactive T cells, the method comprising:
- (1) culturing T cells by a process that comprises:
- (a) incubating a population of cells comprising T cells from a biological sample obtained from a subject that has a tumor with a first T cell stimulatory agent(s) under conditions to stimulate expansion of T cells of the population to produce a population of stimulated T cells;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (d) enriching from the co-culture the population of tumor reactive T cells reactive to the one or more peptides, wherein said tumor-reactive T cells comprise an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- and
- (d) incubating the population of T cells enriched in tumor reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of T cells in the population;
- and
- wherein one or more steps of the culturing is carried out in the presence of at least one T cell adjuvant that is a costimulatory agonist;
- and
- (2) harvesting cells produced by the method to produce a composition of expanded T cells enriched in tumor reactive T cells.
7 more elements
A method for manufacturing tumor reactive T cells, the method comprising:
- (1) culturing T cells by a process comprising:
- (a) incubating a population of cells comprising T cells from a biological sample from a subject that has a tumor with a first T cell stimulatory agent(s) comprising one or more recombinant cytokines under conditions to stimulate expansion of T cells in the population to produce a population of stimulated T cells, wherein the incubation with the one or more recombinant cytokines is in the presence of at least one T cell adjuvant that is a costimulatory agonist;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (c) enriching tumor-reactive T cells from the co-culture, said tumor-reactive T cells comprising an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- (d) incubating the population of T cells enriched for tumor-reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of cells of cells of the population of cells;
- and
- (2) harvesting the expanded cells produced by the method.
4 more elements
A method for manufacturing tumor-reactive T cells, the method comprising:
- (1) culturing T cells by a process that comprises:
- (a) incubating a population of cells comprising T cells from a biological sample obtained from a subject that has a tumor with a first T cell stimulatory agent(s) under conditions to stimulate expansion of T cells of the population to produce a population of stimulated T cells;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (d) enriching from the co-culture the population of tumor reactive T cells reactive to the one or more peptides, wherein said tumor-reactive T cells comprise an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- and
- (d) incubating the population of T cells enriched in tumor reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of T cells in the population;
- and
- wherein one or more steps of the culturing is carried out in the presence of at least one T cell adjuvant that is a checkpoint inhibitor;
- and
- (2) harvesting the expanded cells produced by the method.
7 more elements
A method for manufacturing tumor reactive T cells, the method comprising:
- (1) culturing T cells by a process comprising:
- (a) incubating a population of cells comprising T cells from a biological sample from a subject that has a tumor with a T cell stimulatory agent(s) comprising one or more recombinant cytokines under conditions to stimulate expansion of T cells in the population to produce a population of stimulated T cells, wherein the incubation with the one or more recombinant cytokines is in the presence of at least one T cell adjuvant that is a checkpoint inhibitor ;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (c) enriching tumor-reactive T cells from the co-culture, said tumor-reactive T cells comprising an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- (d) incubating the population of T cells enriched for tumor-reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of cells of cells of the population of cells;
- and
- (2) harvesting the expanded cells produced by the method.
4 more elements
The method of any of claims 6, 7, 10-18, 26, 27 and 36-38, wherein the costimulatory agonist specifically bind GITR. The method of any of claims 6, 7, 10-18, 26, 27, 36-38 and 46, wherein the costimulatory agonist is MK-1248, or is an antigen-binding fragment of any of the foregoing.
A method for manufacturing tumor-reactive T cells, the method comprising:
- (1) culturing T cells by a process that comprises:
- (a) incubating a population of cells comprising T cells from a biological sample obtained from a subject that has a tumor with a first T cell stimulatory agent(s) comprising one or more recombinant cytokine selected from one or more of IL-7, IL-15 and IL-21 under conditions to stimulate expansion of T cells of the population to produce a population of stimulated T cells;
- (b) co-culturing the population of stimulated T cells in the presence of antigen presenting cells (APCs) under conditions in which the APCs have been induced to present one or more peptides from a tumor-associated antigen from the subject, thereby generating a population containing T cells comprising tumor reactive T cells;
- (d) enriching from the co-culture the population of tumor reactive T cells reactive to the one or more peptides, wherein said tumor-reactive T cells comprise an endogenous TCR that is reactive to a tumor-associated antigen, thereby producing a population of T cells enriched for tumor-reactive T cells;
- and
- (d) incubating the population of T cells enriched in tumor reactive T cells with a second T cell stimulatory agent(s) under conditions to stimulate expansion of T cells in the population;
- and
- (2) harvesting the expanded cells produced by the method.
5 more elements
Dependencies are inferred from the claim text.