METHODS FOR IMPROVING THE EFFICACY AND EXPANSION OF CHIMERIC ANTIGEN RECEPTOR?EXPRESSING CELLS
First Claim
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1. A method of enriching for, or making, an immune effector cell (e.g., cell population) suitable for use in a CAR therapy, comprising acquiring (e.g., obtaining or harvesting) the immune effector cell, according to one, two, three, four, five or more (all) of the following:
- (i) the timing of immune effector cell acquisition from a subject (e.g., a hematological cancer patient);
(ii) the timing of the chemotherapy in relation to the immune effector cell acquisition;
(iii) the type of chemotherapy;
(iv) the underlying malignancy;
(v) an immune effector cell (e.g., T cell) parameter, e.g., one or more of T cell number, T cell phenotype or T cell function,or a combination of two, three, four, or five of (i)-(v),thereby enriching for, or making, the immune effector cell suitable for use in a CAR therapy.
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Abstract
The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.
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Citations
70 Claims
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1. A method of enriching for, or making, an immune effector cell (e.g., cell population) suitable for use in a CAR therapy, comprising acquiring (e.g., obtaining or harvesting) the immune effector cell, according to one, two, three, four, five or more (all) of the following:
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(i) the timing of immune effector cell acquisition from a subject (e.g., a hematological cancer patient); (ii) the timing of the chemotherapy in relation to the immune effector cell acquisition; (iii) the type of chemotherapy; (iv) the underlying malignancy; (v) an immune effector cell (e.g., T cell) parameter, e.g., one or more of T cell number, T cell phenotype or T cell function, or a combination of two, three, four, or five of (i)-(v), thereby enriching for, or making, the immune effector cell suitable for use in a CAR therapy. - View Dependent Claims (4, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65)
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2. A composition comprising an immune effector cell (e.g., cell population) that expresses a CAR molecule (a “
- CAR-expressing cell”
) for use, in combination with a chemotherapy, in treating, or in providing anti-tumor immunity to, a subject having a hematological cancer, wherein the immune effector cell is acquired (e.g., obtained or harvested) from the subject, by optimizing one, two, three, four, or more (all) of the following;(i) the timing of immune effector cell acquisition from a subject (e.g., a cancer patient); (ii) the timing of the chemotherapy in relation to the immune effector cell acquisition; (iii) the type of chemotherapy; (iv) the underlying malignancy; (v) an immune effector cell (e.g., T cell) parameter, e.g., one or more of T cell number, T cell phenotype or T cell function, or a combination of two, three, four, or five of (i)-(v), (optionally) wherein the immune effector cell is acquired from the subject prior to introduction of the CAR molecule, - View Dependent Claims (5, 6, 7)
- CAR-expressing cell”
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3. A method of treating, or providing anti-tumor immunity to, a subject having a hematological cancer, comprising administering to the subject an effective amount of an immune effector cell (e.g., a cell population) that expresses a CAR molecule (a “
- CAR-expressing cell”
or a “
CAR therapy”
), in combination with a chemotherapy, wherein the immune effector cell is acquired (e.g., obtained or harvested) from the subject, by optimizing one, two, three, four, or more (all) of the following;(i) the timing of immune effector cell acquisition from a subject (e.g., a cancer patient); (ii) the timing of the chemotherapy in relation to the immune effector cell acquisition; (iii) the type of chemotherapy; (iv) the underlying malignancy; (v) an immune effector cell (e.g., T cell) parameter, e.g., one or more of T cell number, T cell phenotype or T cell function, or a combination of two, three, four, or five of (i)-(v), (optionally) wherein the immune effector cell is acquired from the subject prior to introduction of the CAR molecule, thereby treating, or providing anti-tumor immunity to, the hematological cancer.
- CAR-expressing cell”
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32. The method of claim 231, wherein the acquired immune effector cell population includes at least 20% naï
- ve T cells, at least 2% stem central memory T cells, and/or at least 4% central memory T cells.
- View Dependent Claims (38)
- 66. An immune cell preparation or reaction mixture, e.g., comprising a population of immune effector cells (e.g., comprising a CAR molecule or a nucleic acid encoding a CAR molecule), made according to any of the methods described herein.
Specification