Diagnostic methods for t cell therapy
OwnerAdrian Bot, Jeffrey S. Wiezorek +4inventors
InventorsAdrian Bot, Jeffrey S. Wiezorek, William Go, Rajul Jain, James N. Kochenderfer, Steven A. Rosenberg
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Abstract
The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes methods of identifying a patient who would respond well to a T cell therapy or conditioning a patient prior to a T cell therapy so that the patient responds well to a T cell therapy. The conditioning involves administering one or more preconditioning agents prior to a T cell therapy and identifying biomarker cytokines prior to administering a T cell therapy.
Claims30
A method for treating a leukemia in a subject with chimeric antigen receptor (CAR) T cell therapy comprising:
- (i) administering to the subject one or more preconditioning agents that are capable of increasing a serum level of interleukin-15 (“IL-15”), interleukin-7 (“IL-7”), and any of monocyte chemotactic protein 1 (“MCP-1”), C-reactive protein (CRP), and interferon gamma-induced protein 10 (“IP-10”), wherein the preconditioning agents comprise cyclophosphamide and fludarabine;
- and (ii) administering a therapeutically effective amount of anti-CD19 CAR T cell therapy to the subject on day zero, wherein the subject is determined to exhibit an increase in the serum level at day zero prior to the administration of CAR T cell therapy of IL-15, and IL-7, and any of MCP-1, CRP, and IP-10, relative to their baseline serum levels prior to the administration of the preconditioning agents, wherein the IL-15, IL-7, MCP-1, CRP, and IP-10 serum levels are measured by an enzyme-linked immunosorbent assay (ELISA) or any method that detects the amount of protein in the serum for each protein and allows for their quantification, and wherein the serum level of IL-15 is increased by at least 5-fold.
A method for identifying a subject as having an improved response to anti-CD19 CAR T cell therapy comprising (i) administering to the subject one or more preconditioning agents that are capable of increasing the serum level of IL-15 and IL-7, and any of MCP-1, CRP, and IP-10, wherein the preconditioning agents comprise cyclophosphamide and fludarabine;
- (ii) measuring the serum levels of IL-15, IL-7, and any of MCP-1, CRP, and IP-10 at baseline, which is prior to the administration of the preconditioning agent(s), and their serum levels at day zero, which is after administration of the preconditioning agent(s) and prior to, but on the day of, administration of CAR T cell therapy;
- wherein the IL-15, IL-7, and any of MCP-1, CRP, and IP-10 serum levels are measured by an enzyme-linked immunosorbent assay (ELISA) or any method that detects the amount of protein in the serum for each protein and allows for their quantification;
- and wherein the subject is identified as having an improved response to fer anti-CD19 CAR T cell therapy if there is an increase in the serum levels of IL-15 and IL-7, and any of MCP-1, CRP, and IP-10 at day zero, prior to the administration of CAR T cell therapy and relative to their baseline serum levels;
- and (ii) administering to the subject anti-CD19 CAR T cell therapy, wherein the subject has leukemia, and wherein the serum level of IL-15 is increased by at least 5-fold.
A method for increasing a serum level of IL-15 and IL-7 and any of MCP-1, CRP, and IP-10 to pre-condition a subject in need of anti-CD19 CAR T cell therapy comprising administering to the subject one or more preconditioning agents, wherein the subject is treated with anti-CD19 CAR T cell therapy at day zero when exhibiting an increase in the serum level of IL-15 and IL-7, and any of MCP-1, CRP, and IP-10 prior to, but on the day of administration of the therapy, relative to baseline levels prior to pre-conditioning, wherein IL-15, IL-7, and any of MCP-1, CRP, and IP-10 serum levels are measured by an enzyme-linked immunosorbent assay (ELISA) or any method that detects the amount of protein in the serum for each protein and allows for their quantification;
- wherein the preconditioning agents comprise cyclophosphamide and fludarabine, wherein the subject has leukemia, and wherein the serum level of IL-15 is increased by at least 5-fold.
Dependencies are inferred from the claim text.