Methods of making chimeric antigen receptor-expressing cells
AssigneesNovartis AG, The Trustees of the University of Pennsylvania
InventorsJoseph A. Fraietta, Jan J. Melenhorst, Elena Orlando, Roderick O'Connor, Carl H. June
Life of this patent
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Abstract
The disclosure provides methods of making CAR-expressing immune effector cells (e.g., T cells, or NK cells), and compositions and reaction mixtures comprising the same. The disclosure further provides methods of using said CAR-expressing immune effector cells.
Claims28
A method of making a population of Chimeric Antigen Receptor (CAR)-expressing immune effector cells, comprising:
- a) providing a population of immune effector cells;
- b) contacting the population of immune effector cells with a nucleic acid encoding a CAR polypeptide;
- c) contacting the population of immune effector cells with a Stat3 activator;
- and
- d) maintaining the cells under conditions that allow expression of the CAR polypeptide,
- thereby making a population of CAR-expressing immune effector cells.
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A method of making a population of Chimeric Antigen Receptor (CAR)-expressing immune effector cells, comprising:
- a) providing a population of immune effector cells;
- b) contacting the population of immune effector cells with a nucleic acid encoding a CAR polypeptide;
- c) contacting the population of immune effector cells with an inhibitor of glycolysis, and
- d) maintaining the cells under conditions that allow expression of the CAR polypeptide, thereby making a population of CAR-expressing immune effector cells.
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A reaction mixture comprising:
- a) (i) a population of CAR-expressing immune effector cells or (ii) an immune effector cell and a nucleic acid encoding a CAR;
- and
- b) an agent selected from:
- (i) a Stat3 activator;
- (ii) a gp130 molecule or a Stat3 molecule, or nucleic acid encoding a gp130 molecule or a Stat3 molecule;
- or
- (iii) an inhibitor of glycolysis.
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A method of evaluating or predicting the responsiveness of a subject having a cancer, to a therapeutic treatment with a CAR-expressing cell, comprising evaluating in an immune effector cell from the subject, or wherein the subject has been treated with a CAR-expressing cell, comprising evaluating tin a CAR-expressing cell from the subject:
- i) a level of glucose metabolism, wherein:
- a level of glucose metabolism that is lower than a glucose metabolism reference value is indicative that the subject is likely to respond to treatment with the CAR-expressing cell, and
- a level of glucose metabolism that is higher than a glucose metabolism reference value is indicative that the subject is less likely to respond to treatment with the CAR-expressing cell;
- or
- ii) a level of Stat3 activation as measured by phosphorylation of Stat3 or level or activity of Stat3 transcriptional targets wherein:
- a level of Stat3 activation that is higher than a Stat3 activation reference value is indicative that the subject is likely to respond to treatment with the CAR-expressing cell, and
- a level of Stat3 activation that is lower than a Stat3 activation reference value is indicative that the subject is less likely to respond to treatment with the CAR-expressing cell,
- thereby evaluating the subject or predicting the responsiveness of the subject to the CAR-expressing cell.
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Dependencies are inferred from the claim text.