COMBINATIONS OF LOW, IMMUNE ENHANCING, DOSES OF MTOR INHIBITORS AND CARS
First Claim
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1. A method of treating a subject in need thereof comprising administering to the subject an mTOR inhibitor, wherein said mTOR inhibitor enhances an immune response of said subject, and wherein said subject has received, is receiving or is about to receive an immune effector cell engineered to express a CAR.
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Abstract
The invention relates, in part, to a method of treating a subject comprising administering to the subject a low, immune enhancing of a mTOR inhibitor and an immune effector cell engineered to express a CAR.
47 Citations
47 Claims
- 1. A method of treating a subject in need thereof comprising administering to the subject an mTOR inhibitor, wherein said mTOR inhibitor enhances an immune response of said subject, and wherein said subject has received, is receiving or is about to receive an immune effector cell engineered to express a CAR.
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3. A method of making an immune effector cell, having disposed therein a nucleic acid encoding a CAR, comprising:
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a) contacting an immune effector cell with an mTOR inhibitor; and b) inserting a nucleic acid that encodes the CAR into the immune effector cell; thereby making an immune effector cell, having disposed therein a nucleic acid encoding a CAR, wherein said contacting of step a) occurs prior to, concurrently with, or after said inserting of step b); and wherein the mTOR inhibitor causes one or more of the following to occur; 1a) an increase in the proportion of PD-1 negative immune effector cells; 1b) a decrease in the proportion of PD-1 positive immune effector cells; 1c) an increase in the ratio of PD-1 negative immune effector cells/PD-1 positive immune effector cells; 1d) an increase in the number of naï
ve T cells;1e) an increase in the expression of one or more of the following markers;
CD62Lhigh, CD127high, CD27+, and BCL2;1f) a decrease in the expression of KLRG1;
or1g) an increase in the number of memory T cell precursors. - View Dependent Claims (4)
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5. A method of making an immune effector cell, having disposed therein a nucleic acid encoding a CAR, comprising:
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a) providing an immune effector cell made by; i) administering to a subject an mTOR inhibitor for an amount of time sufficient for one or more of the following to occur; 1a) an increase in the proportion of PD-1 negative immune effector cells; 1b) a decrease in the proportion of PD-1 positive immune effector cells; 1c) an increase in the ratio of PD-1 negative immune effector cells/PD-1 positive immune effector cells; 1d) an increase in the number of naï
ve T cells;1e) an increase in the expression of one or more of the following markers;
CD62Lhigh, CD127high, CD27+, and BCL2;1f) a decrease in the expression of KLRG1;
or1g) an increase in the number of memory T cell precursors; and (ii) collecting the immune effector cell from the subject; and b) inserting a nucleic acid that encodes the CAR into the collected immune effector cell, thereby making an immune effector cell, having disposed therein a nucleic acid encoding a CAR. - View Dependent Claims (45)
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41-42. -42. (canceled)
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46. (canceled)
Specification